Exposure to second-hand tobacco smoke and respiratory symptoms in non-smoking adults: cross-sectional data from the general population of Telemark, Norway.

BACKGROUND: In Norway, data on the association between second-hand tobacco smoke (SHS) exposure at home and respiratory symptoms in adults are limited. METHODS: We assessed the association between self-reported exposure to SHS and the prevalence of respiratory symptoms among never-smokers aged 16 to 50 years from the general population who were included in a cross-sectional population-based study in Telemark County, Norway. Logistic regression analysis was used to estimate the odds ratios of symptoms among 8850 never-smokers who provided an affirmative response to questions regarding SHS; 504 (5.7%) of these reported that they lived in a home with daily or occasional indoor smoking. RESULTS: Productive cough and nocturnal dyspnoea were statistically associated with daily SHS exposure (ORs 1.5 [95% CI 1.04-2.0] and 1.8 [1.2-2.7], respectively). In analyses stratified by gender, nocturnal dyspnoea was associated with SHS among women (OR 1.8 [1.1-3.1]), but not among men (OR 0.93 [0.49-1.8]). Symptoms were not associated with occasional SHS exposure in the entire group, but infrequent exposure among men only was associated with increased prevalence of chronic cough; (OR 1.6; [1.04-2.6]) and was negatively associated with wheeze; (OR 0.44 [0.21-0.92)]. CONCLUSIONS: Daily SHS exposure in private homes was associated with productive cough and nocturnal dyspnoea. Our results suggest that preventive measures may be needed to reduce the respiratory effects of SHS at home. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073708 Registered February 27. 2014.

Association of respiratory symptoms and asthma with occupational exposures: findings from a population-based cross-sectional survey in Telemark, Norway.

OBJECTIVES: The aim of this study was to estimate the prevalence of respiratory symptoms and physician-diagnosed asthma and assess the impact of current occupational exposure. DESIGN: Cross-sectional analyses of the prevalence of self-reported respiratory health and association with current occupational exposure in a random sample of the general population in Telemark County, Norway. SETTINGS: In 2013, a self-administered questionnaire was mailed to a random sample of the general population, aged 16-50, in Telemark, Norway. The overall response rate was 33%, comprising 16 099 responders. OUTCOME MEASURES: The prevalence for respiratory symptoms and asthma, and OR of respiratory symptoms and asthma for occupational groups and exposures were calculated. Occupational exposures were assessed using self-reported exposure and an asthma-specific job-exposure matrix (JEM). RESULTS: The prevalence of physician-diagnosed asthma was 11.5%. For the occupational groups, the category with agriculture/fishery workers and craft/related trade workers was associated with wheezing and asthma attack in the past 12 months, showing OR 1.3 (1.1 to 1.6) and 1.9 (1.2 to 2.8), respectively. The group including technicians and associated professionals was also associated with wheezing OR 1.2 (1.0 to 1.3) and asthma attack OR 1.4 (1.1 to 1.9). The JEM data show that exposure to flour was associated with wheezing OR 3.2 (1.4 to 7.3) and woken with dyspnoea OR 3.5 (1.3 to 9.5), whereas exposures to diisocyanates, welding/soldering fumes and exposure to vehicle/motor exhaust were associated with dyspnoea OR 2.9 (1.5 to 5.7), 3.2 (1.6 to 6.4) and 1.4 (1.0 to 1.8), respectively. CONCLUSIONS: The observed prevalence of physician-diagnosed asthma was 11.5%. The 'manual' occupations were associated with respiratory symptoms. Occupational exposure to flour, diisocyanates, welding/soldering fumes and vehicle/motor exhaust was associated with respiratory symptoms in the past 12 months and use of asthma medication. However, prospective data are needed to confirm the observed associations.

Breath-taking jobs: a case-control study of respiratory work disability by occupation in Norway.

BACKGROUND: The current knowledge on respiratory work disability is based on studies that used crude categories of exposure. This may lead to a loss of power, and does not provide sufficient information to allow targeted workplace interventions and follow-up of patients with respiratory symptoms. OBJECTIVES: The aim of this study was to identify occupations and specific exposures associated with respiratory work disability. METHODS: In 2013, a self-administered questionnaire was mailed to a random sample of the general population, aged 16-50, in Telemark County, Norway. We defined respiratory work disability as a positive response to the survey question: 'Have you ever had to change or leave your job because it affected your breathing?' Occupational exposures were assessed using an asthma-specific job-exposure matrix, and comparison of risks was made for cases and a median of 50 controls per case. RESULTS: 247 workers had changed their work because of respiratory symptoms, accounting for 1.7% of the respondents ever employed. The 'breath-taking jobs' were cooks/chefs: adjusted OR 3.6 (95% CI 1.6 to 8.0); welders: 5.2 (2.0 to 14); gardeners: 4.5 (1.3 to 15); sheet metal workers: 5.4 (2.0 to 14); cleaners: 5.0 (2.2 to 11); hairdressers: 6.4 (2.5 to 17); and agricultural labourers: 7.4 (2.5 to 22). Job changes were also associated with a variety of occupational exposures, with some differences between men and women. CONCLUSIONS: Self-report and job-exposure matrix data showed similar findings. For the occupations and exposures associated with job change, preventive measures should be implemented.

Neosporosis in a captive Parma wallaby (Macropus parma).

Infection with Neospora caninum has been diagnosed in a variety of animal species; however, reports in marsupials are rare. A captive Parma wallaby (Macropus parma) died suddenly and was subjected to necropsy examination. The main finding was necrotizing myocarditis associated with protozoan parasites. The protozoa were identified as N. caninum by use of immunohistochemistry and partial gene sequence analysis. Neospora and Toxoplasma should be considered a possible cause of disease in captive marsupials. Further work is required to determine whether marsupials are an accidental or terminal host of this protozoan in order to better understand the host-parasite relationship.

Exposure to thoracic dust, airway symptoms and lung function in cement production workers.

Cement dust exposure has previously been associated with airway symptoms and ventilatory impairment. The aim of the present study was to examine lung function and airway symptoms among employees in different jobs and at different levels of exposure to thoracic dust in the cement production industry. At the start of a 4-yr prospective cohort study in 2007, exposure to cement dust, symptoms and lung function were recorded cross-sectionally in 4,265 employees in 24 European cement plants. Bronchial exposure was assessed by 2,670 full-shift dust samples with cyclones collecting the thoracic aerosol fraction. A job exposure matrix was constructed by grouping dust concentrations according to job type and plant. Elevated odds ratios for symptoms and airflow limitation (range 1.2-2.6 in the highest quartile), but not for chronic bronchitis, were found in the higher quartiles of exposure compared with the lowest quartile. Forced expiratory volume in 1 s (FEV(1)) showed an exposure-response relationship with a 270-mL deficit of FEV(1) (95% CI 190-300 mL) in the highest compared with the lowest exposure level. The results support the hypothesis that exposure to dust in cement production may lead to respiratory symptoms and airway obstruction.

High-resolution method for regulatory control of Echinacea species in Nutraceuticals by CD-MEKC.

One problem in the international regulatory control of Echinacea, a therapeutic Nutraceutical, is recognition of caffeoyl solutes and alkamides in different products. Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) has been applied to Echinacea spp. in combination with pattern recognition of some caffeoyl solutes. A novel metric based on relative migration time (RMT) data has been developed in CE to address the problem of variable reported migration time. The CD-MEKC method of Gotti's group using hydroxypropyl-beta-cyclodexrin (HP-beta-CD; 100 mM) with sodium dodecyl sulphate (SDS; 110 mM), in a triacid background electrolyte (10 mM, pH 8) under 19 kV was adapted to identify two key hydrophilic solutes: chlorogenic acid and cichoric acid present in all commercial products. Two internal markers were taken as reference points to calculate the RMT of any target peak: RMT=t(m (target))/t(m (marker)). The RMT method was robust to temperature change from 20 to 40 degrees C, but sensitive to pH. The lateral shift and reproducibility of the target peak t(m (target)) were significantly reduced by this novel transformation. In the worst cases migration time variability ranged up to 12% (n=6); the RMT algorithm reduced this to less than 1%. In general, the RMT transformation reduced the variability of migration time data by a factor of 2-5. For systematic comparison of electrophoretic profiles for test sample and standard, a new pattern recognition algorithm permits sequential peak-by-peak comparison using specified segments of the electropherograms for comparison of test and Echinacea purpurea (root product) as a standard. This algorithm was capable of rapidly characterising the similarity of target peaks in a test sample relative to those in the reference standard. Combination of the RMT algorithm and pattern recognition in CE is expected to offer a robust approach to international regulatory characterisation and control of Nutraceuticals.

[Rheophoresis. A systematic approach to therapy of age-related macular degeneration (AMD)?]. / Rheopherese Ein systemischer Therapieansatz für die altersabhängige Makuladegeneration (AMD)?

BACKGROUND: Choroidal microcirculation is impaired in age-related macular degeneration (AMD), and leads to deposition of lipids and proteins in Bruch's membrane. Rheophoresis can improve choroidal microcirculation by eliminating high molecular weight, rheologically relevant plasma proteins. The objective of this post-certification study was to analyse the effect of rheophoresis in 10 AMD patients. PATIENTS AND METHODS: A total of 6 patients with early AMD and 4 with late AMD in one eye (initial visual acuity equivalent 0.2-0.8) received rheophoresis treatment 10 times over an 18-week period. Visual acuity and color vision were determined initially and after 3, 5 and 12 months and fluorescein angiography was performed. RESULTS: Patients with early AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 2 out of 6 cases and a stable visual acuity in 4 out of 6 cases 1 year after rheophoresis, whereas patients with late AMD showed improvement of visual acuity (2 lines on ETDRS charts) in 1 out of 4 cases and a stable visual acuity in 3 out of 4 cases. In red-free fundus photography, a reduction in drusen size and number could be observed in 4 out of 10 cases. CONCLUSION: The results of this investigation seem to be in accordance with data from previously published controlled clinical trials. Recommendations for the indication of rheopheresis for AMD should be further defined and evaluated within the framework base of a multicentric cooperative study.

Separation of the voriconazole stereoisomers by capillary electrophoresis and liquid chromatography.

A chiral capillary electrophoresis (CE) method has been developed for the direct separation of the four stereoisomers of a new broad spectrum antifungal agent, voriconazole. Cyclodextrin (CD) modified micellar electrokinetic chromatography employing, alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD was not sufficiently selective for the four neutral stereoisomers. Three anionic sulphobutyl-ether-beta-CD (SBE-beta-CD) electrolyte additives, each having a defined degree of substitution (DS) (6.5, 4.5 and 1.0) were subsequently examined. The complete CE separation of all four stereoisomers was obtained when using the medium substituted additive DS = 4.5. In liquid chromatography (LC), two approaches were examined for the direct chiral separation of the stereoisomers of voriconazole: (a) use of the neutral and anionic CD mobile phase additives and (b) a vancomycin chiral stationary phase. The CD additives were shown to be extremely selective for two stereoisomers of voriconazole (active drug and its enantiomer) but unable to discriminate between the opposite two stereoisomers. The converse was observed, however, when the vancomycin chiral stationary phase was employed.

High-performance liquid chromatography study of stereospecific microsomal enzymes catalysing the reduction of a potential cytostatic drug, oracin. Interspecies comparison.

One of the main metabolites of oracin (I) ¿6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno[1,2- c] isoquinoline¿, a potential cytostatic drug, is 11-dihydrooracin (II) ¿(+),(-)-6-[2-(2-hydroxyethyl)aminoethyl]-5-oxo-11-hydroxy-5,6-dihydro-1 1H- indeno[1,2-c]isoquinoline¿, a metabolite formed by the reduction of oracin's pro-chiral centre on C 11. This metabolite has been found in all laboratory species in vitro and in vivo and it constitutes the main metabolite in man. The stereospecificity of reducing enzymes participating in the oracin biotransformation pathway was investigated using microsomal preparations from standard laboratory animals. Enzyme stereospecificity has been defined as preferential formation by the enzyme of the (+) or (-) stereoisomer of II. Significant interspecies differences were observed in the stereospecificity of the respective biotransformation enzymes. HPLC quantitative determinations of both enantiomers were performed using a Chiralcel OD-R column as chiral stationary phase with excellent resolution and stability.

Immunity to asexual blood stages of Plasmodium: is resistance to acute malaria adaptive or innate?

Current models of immunity to blood stages of Plasmodium invoke a primary role for T-cell dependent processes and much recent evidence implicates Th1-type responses as crucial to the control of acute malaria. But do these data stand up to close scrutiny? Here, Andy Fell and Nick Smith review recent data from rodent and human studies and suggest that Th1-type responses may not after all be important in controlling malaria infection in the blood.

Use of 1H-NMR spectroscopy to determine the enantioselective mechanism of neutral and anionic cyclodextrins in capillary electrophoresis.

One-dimensional (ID) and two-dimensional (2D) 1H nuclear magnetic resonance (NMR) techniques have been used to investigate the chiral recognition process in capillary electrophoresis (CE) for seven different cyclodextrins (CDs) with the calcium channel blocker amlodipine as a model compound. These include five neutral CDs (alpha-CD, beta-CD, gamma-CD, hydroxypropyl-beta-CD and hydroxyethyl-beta-CD) and two anionic CDs (sulphobutyl-ether-beta-CD and carboxymethyl-beta-CD) where mixtures of amlodipine with each of the seven CDs were examined by 1D NMR in deuterated phosphate buffer at pD 3.4. The resonance shift of signals with added CD, relative to the CD-free position (shift displacement, delta delta) and shift non-equivalence (delta delta *) of enantiomeric signals shifted relative to each other after addition of CD were examined for non-overlapped protons of amlodipine. The possible correlations of NMR shift non-equivalence data with chiral separation in CE for amlodipine have been critically assessed. Qualitative differences in the 1D NMR shifts and enhanced enantioselectivity in CE were observed for amlodipine with sulphobutyl-ether-beta-CD. Further experiments on the through-space interactions using 2D rotating frame nuclear Overhauser effect spectroscopy (ROESY) indicated that there was no association between internal glucopyranose hydrogen atoms and the aromatic hydrogens of amlodipine. This gives evidence for the aromatic ring not being included in this CD. Moreover, data from spin-lattice relaxation times (T1) measured for amlodipine in the free state and after addition of the anionic sulphobutyl-ether-beta-CD indicate that the aromatic moiety of amlodipine is not included into the sulphobutyl-ether-beta-CD cavity. There is evidence that it interacts with the sulphobutyl side chains, and may adopt a preferred orientation outside the sulphobutyl-ether-beta-CD toroid itself.

A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy.

The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.

Separation of the stereoisomers of the main metabolite of a non-steroidal anti-inflammatory drug, flobufen, by chiral high-performance liquid chromatography.

The major metabolite of a novel non-steroidal anti-inflammatory drug, DL-4-(2',4'-difluorobiphenyl-4-yl)-2-oxo-2-methylbutanoic acid (flobufen, I), namely 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-gamma-butyrolactone (4-dihydroflobufen lactone, III), has four stereoisomers consisting of two racemic pairs of enantiomers. Of three chiral stationary phases tested, Cyclobond I beta-RSP (Astec) (beta-cylodextrin derivatized with R,S-hydroxypropyl) was best able to separate the (+2)(--) racemate, with a liquid phase containing acetonitrile as modifier and triethylamine acetate as buffer. Using the Box-Wilson Central Composite Design for three factors, an optimum combination of pH and concentrations of the modifier and buffer was eventually obtained. A chromatographic response function based on a combination of the Kaiser peak separation function, Pi, and retention time of the second eluting enantiomer, tRL, served as a response criterion for the process of optimization. The optimum conditions developed for the (+2)(--) racemate were also found to be suitable for separating the (+-)(-+) racemate, for which earlier studies had shown the separation to be more facile. Separation of the four stereoisomers of III, for which the chiral chromatographic system optimized in this study is proposed as the second stage, is targeted at a biochemical study of the stereoisomeric metabolism of I.

Chiral recognition in liquid chromatography utilising chargeable cyclodextrins for resolution of doxazosin enantiomers.

The chromatographic resolution of rac-doxazosin using reversed-phase high performance liquid chromatography (HPLC) with the chargeable chiral mobile phase additive, carboxymethyl-beta-cyclodextrin (CM-beta-CD), is described. The effects of different modifiers (acetonitrile, methanol and tetrahydrofuran), pH, temperature, and cyclodextrin concentration were investigated to a) assess the key chromatographic parameters for subsequent chemometric optimisation, and b) explore the enantioselective mechanism. Assuming a 1:1 complex between each doxazosin enantiomer and CM-beta-CD, studies of the relationship between the capacity factors (k') and functions of CM-beta-CD concentration indicate that the mechanisms for retention and chiral selectivity are comparable with those proposed earlier by Sybilska et al. Stability constants (KG) calculated for rac-doxazosin complexed with CM-beta-CD (647 +/- 55 and 594 +/- 45 M-1 for each enantiomer respectively) are significantly larger than those calculated for the barbiturates complexed with beta-CD (ca. 101-108 M-1). Investigations on pH indicate an ionic or ino-pair interaction between the anionic CM-beta-CD and the cationic doxazosin enantiomers. A central composite design was used to optimise the key chromatographic parameters: pH, methanol (v/v) and CM-beta-CD concentration. The Kaiser peak separation index, Pi, was used for the response function. The predicted response for this chiral separation has been compared with that observed experimentally and samples of the four-dimensional response surface have been assessed for their value in showing robustness.

Plasmodium falciparum-specific T cell clones from non-exposed and exposed donors are highly diverse in TCR beta chain V segment usage.

Humans lacking previous exposure to Plasmodium falciparum typically have a high frequency of malaria-reactive T cells in peripheral blood, which cross-react with antigens from other microorganisms. We studied a large number of malaria-specific human T cell clones from non-exposed and malaria-exposed donors to determine whether this response is oligoclonal, and might therefore be generated by a limited number of cross-reactive epitopes. Most clones responded well to schizont antigen from three antigenically distinct stocks of P. falciparum. Clones derived from the same donor tended to show similar patterns of reactivity to a panel of non-malaria antigens from various microorganisms, suggesting that a limited number of epitopes were recognized by individuals. However, analysis of the usage of V segments of the beta chain of the TCR (TCRBV) revealed no evidence of TCRBV restriction in the T cell response, either within individual donors or across all donors. An apparent skewing towards TCRBV8 in one donor was shown by two methods to be due to in vitro expansion of a single clone: (i) Direct sorting of TCRBV8+ CD4+ T cells from fresh PBMC did not reveal any enrichment for pRBC-reactive cells; (ii) Sequencing of VDJ regions revealed that the TCRBV8 clones were identical. Sequences of non-TCRBV8 clones from this donor showed major differences in the VDJ junctional region. No differences in TCRBV repertoire between non-exposed and exposed donors were observed. These results exclude the existence of a malarial superantigen and suggest that the T cell response to malaria schizont antigen in non-exposed donors is driven by a large number of epitopes.

Determination of plasma concentrations of epirubicin and its metabolites by high-performance liquid chromatography during a 96-h infusion in cancer chemotherapy.

In order to determine epirubicin and its metabolites at low concentrations (< 38 ng/ml) in small plasma samples, a fast reliable method based on a precipitation pre-treatment and sensitive reversed-phase isocratic HPLC has been developed and validated for epirubicin in the range 5-100 ng/ml. The R.S.D. was 5-9% over this concentration range. For human serum containing 25 ng/ml of epirubicin, the inter- and intra-day variation was < 10%. Recoveries of the metabolites epirubicinol, 7-deoxydoxorubicinone and 7-deoxydoxorubicinolone at 20 ng/ml ranged from 94-104%. The assay has been used to study human plasma samples taken during a 96-h infusion of epirubicin in a patient with multiple myeloma. The combined levels of the unseparated metabolites, epirubicin glucuronide and epirubicinol glucuronide, were semiquantitatively determined after treatment with beta-glucuronidase. The metabolites epirubicinol and 7-deoxydoxorubicinolone, but not 7-deoxydoxorubicinone, were also detected and measured.

Method development in liquid chromatography with a charged cyclodextrin additive for chiral resolution of rac-amlodipine utilising a central composite design.

A negatively charged derivative of beta-cyclodextrin, sulphobutyl ether-beta-cyclodextrin (SBE-beta-CD), was examined as a chiral mobile phase additive in reversed-phase high-performance liquid chromatography for the enantiomeric resolution of the calcium channel blocker rac-amlodipine. Theoretical and practical aspects are discussed for setting up a central composite design applicable to any analytical method. These include the correct location of factor points for maintaining orthogonality within the design and the augmentation of centrepoint experiments to allow a larger factor space by increasing the distance of axial star points. Optimised separation was achieved using a reverse-phase column with eluent comprising: acetonitrile (ACN)-potassium dihydrogen phosphate (pH 3.93) containing 2.66 mM SBE-beta-CD (26.5:73.5% v/v) at a flow rate of 1.0 ml/min. This yielded a Kaiser peak separation index, Pi = 0.96, at tR2 = 52 min with satisfactory reproducibility, relative standard deviation values: tR1, 0.39%; tR2, 0.47% (n = 5). These experimental results were in excellent agreement with those predicted by the SAS software package for a chromatographic response function model. Multiple regression analysis in four dimensions, with three response models based on Rs, Pi, and a function of Pi, produced response surfaces which revealed zones of optimum robustness and illustrated the interactions involved between the key chromatographic factors. Putative proposals for a mechanism involving the interaction of each of the positively charged enantiomers with the negatively charged cyclodextrin are also discussed. These examine the possibility of ion-pairing and inclusion phenomena to account for the excellent resolution observed.

Delay of copper-catalyzed oxidation of low density lipoprotein by in vitro enrichment with choline or ethanolamine plasmalogens.

Low density lipoprotein (LDL) isolated from human serum of different donors was enriched with plasmalogens and their diacyl analogs in order to investigate a possible effect of these phospholipids on the rate of lipid peroxidation in this lipoprotein. LDL was incubated with either vesicles of choline plasmalogen or phosphatidylcholine in presence of lipoprotein- deficient serum, or with liposomes of ethanolamine plasmalogen or phosphatidylethanolamine together with the non-specific phospholipid transfer protein isolated from beef liver. After re-isolation of LDL by ultracentrifugation, a dose-dependent incorporation of the exogenous phospholipids was obtained. Enrichment of LDL with choline plasmalogen resulted in a delay of the copper-catalyzed oxidation of LDL from five different donors. LDL from two donors was also enriched with diacylglycerophosphocholine which led to a delay of oxidation, but the protective effect was smaller than with choline plasmalogen. Enrichment of LDL from two additional donors with ethanolamine plasmalogen resulted in the strongest protection against oxidation, whereas, diacylglycerophospho-ethanolamine had little effect. The delay of the copper-catalyzed LDL oxidation may be due to a direct antioxidative action of the plasmalogens, which are partially degraded during the lag phase of oxidation, or to an indirect effect caused by alteration of the LDL surface in the presence of an excess of glycerophospholipids.