Subfraction Concentrations Research Articles

The distribution and δ34S values of organic sulfur compounds in biodegraded oils from Peace River (Alberta Basin, western Canada)

The heavy sulfur-rich oils of the Peace River oil sands were formed by severe anaerobic biodegradation. To investigate the impacts of biodegradation on organic sulfur compounds (OSCs) we have measured the distribution and δ34S values of alkylated thioaromatics detected in four oils from each of two Peace River wells (A and B). The fluid composition of the Peace River oil sands can be highly complex due to the variable contributions of sources, thermal maturity and secondary alteration. Nevertheless, a previous multi-molecular investigation of samples from well B oils (PR2 oil-leg of Marcano et al., 2013, Organic Geochemistry 59, 114–132) indicated that the oils had biodegradation levels (BLs) of 5–6, with biodegradation increasing down the oil column. The hydrocarbon composition of oils isolated from well A were biodegraded to a lesser degree than well B (i.e., the presence of isoprenoids and high molecular weight [MW] n-alkanes suggests BLs of ∼3–4). The concentrations of C1–C3 alkylated benzothiophenes (BTs) and C1–C3 alkylated dibenzothiophenes (DBTs) declined sharply through both wells consistent with increased biodegradation, although other alteration impacts (e.g., water washing) might also contribute. The rates of decrease recorded for selected isomers showed variable responses (e.g., 3&4-mBT > 2-mBT; 4-eDBT > 1,3-dmDBT) which implies different susceptibilities to biodegradation and which may contribute additional useful molecular parameters for evaluating the BL of biodegraded S-rich petroleum. The S-isotopic measurements showed a 34S enrichment in several alkyl BTs down the oil leg in well B, with their δ34S values increasing by up to 6‰, consistent with the microbial utilisation of 32S (n.b., the δ34S values of alkyl BTs were not measured in well A oils because of low aromatic sub-fraction concentrations). In contrast, there was little variation in the δ34S values of alkyl DBTs down both wells indicating negligible S-isotopic fractionation of these OSCs in the deeper more biodegraded oils, possibly because of their higher MW and resistance to biodegradation. The δ34SDBT (and bulk δ34S) values of the well B oils were generally slightly enriched than the well A oils probably due to differences in the relative contribution of the major Devonian and Jurassic source rocks.

Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration

Disturbance in lipid metabolism has been suggested as a major pathogenic factor for age-related macular degeneration (AMD). Conventional lipid measures have been inconsistently associated with AMD. Other factors that can alter lipid metabolism include lipoprotein phenotype and genetic mutations. We performed a case-control study to examine the association between lipoprotein profile and neovascular AMD (nAMD) and whether the cholesterylester transfer protein (CETP) D442G mutation modulates these associations. Patients with nAMD had significantly higher concentrations of HDL and IDL compared with controls. The increase in HDL particles in nAMD patients was driven by an excess of medium-sized particles. Concurrently, patients with nAMD also had lower Apo A-1, lower VLDL and chylomicron lipoprotein. Many of these associations showed a dose-dependent association between controls, early AMD cases, and nAMD cases. Adjustment for the presence of the D442G mutation at the CETP locus did not significantly alter the increased AMD risk associated with HDL particle concentration. AMD is associated with variation in many lipoprotein subclasses, including increased HDL and IDL particles and decreased Apo A-1, VLDL, and chylomicron particles. These data suggest widespread systemic disturbance in lipid metabolism in the pathogenesis of AMD, including possible alterations in lipoprotein carrier capacity.

Low IDL-B and high LDL-1 subfraction levels in serum of ALS patients

IntroductionConverging evidence highlights that lipid metabolism plays a key role in ALS pathophysiology. Dyslipidemia has been described in ALS patients and may be protective but peripheral lipoprotein subclasses have never been studied. Material and methodsWe collected sera from 30 ALS patients and 30 gender and age-matched controls. We analyzed 11 distinct lipoprotein subclasses by linear polyacrylamide gel electrophoresis (Lipoprint, Quantimetrix Corporation, USA). We also measured lipoprotein (a), apolipoprotein B, and apolipoprotein E levels. ResultsALS patients had significant higher total cholesterol, HDL-cholesterol, and LDL-cholesterol levels than controls (p<0.0001, p=0.0007, and p=0.0065, respectively). The LDL-1 subfraction concentration was higher (1.03±0.41 vs. 0.71±0.28mmol/L; p=0.0006) and the IDL-B subfraction lower (6.5±2% vs. 8.0±2%; p=0.001) in ALS patients than controls. DiscussionOur preliminary work confirmed the association between ALS and dyslipidemia. The low IDL-B levels may explain the hepatic steatosis frequently reported in ALS. The high levels of the cholesterol-rich LDL-1 subfraction is consistent with previously reported hypercholesterolemia. ConclusionThis study describes, for the first time, the distribution of serum lipoproteins in ALS patients, with low IDL-B and high LDL-1 subfraction level.

Determination of proteins in blood. Part 3: Systematization of methods for the determination of protein compounds in blood

The review presents a chronological development of procedures for determining the concentrations of total protein and albumin; total concentration of globulins; concentrations of subfractions, classes, and subclasses of globulins; and total concentrations of globulin subclasses in human blood. A brief overview of these procedures and the results of their comparative tests in medical examination of patients are given. The considered procedures are systematized; their advantages and disadvantages are discussed. It is noted that procedures for measuring the concentration of total protein, albumin, and globulin classes in plasma, serum, and whole blood are widely used in modern clinical diagnostic laboratories when performing routine assays. The concentrations of globulin subclasses and total concentrations of globulin subclasses in blood are mainly determined in biomedical research. Procedures for measuring the concentration of total globulins and globulin subfractions in plasma and serum are of historical importance and now are barely applied in clinical and diagnostic laboratories.

Determination of proteins in blood. Part 2: Determination of globulins

The review presents the chronological development of procedures for determining the concentrations of total protein and albumin; total concentration of globulins; concentrations of subfractions, classes, and subclasses of globulins; and total concentrations of globulin subclasses in human blood. A brief overview of these procedures and the results of their comparative tests in medical examination of patients are given. The considered procedures are systematized; their advantages and disadvantages are discussed. It is noted that procedures for measuring the concentration of total protein, albumin, and globulin classes in plasma, serum, and whole blood are widely used in modern clinical diagnostic laboratories when performing routine assays. The concentrations of globulin subclasses and total concentrations of globulin subclasses in blood are mainly determined in biomedical research. Procedures for measuring the concentration of total globulins and globulin subfractions in plasma and serum are of historical importance and now are barely applied in clinical and diagnostic laboratories.

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity.

A major goal of biomedicine is to understand the function of every gene in the human genome.1 Loss-of-function (LoF) mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such ‘human knockouts’ can provide insight into gene function. Consanguineous unions are more likely to result in offspring who carry LoF mutations in a homozygous state. In Pakistan, consanguinity rates are notably high.2 Here, we sequenced the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS) designed to understand the determinants of cardiometabolic diseases in South Asians.3 We identified individuals carrying predicted LoF (pLoF) mutations in the homozygous state, and performed phenotypic analysis involving >200 biochemical and disease traits. We enumerated 49,138 rare (<1 % minor allele frequency) pLoF mutations. These pLoF mutations are predicted to knock out 1,317 genes in at least one participant. Homozygosity for pLoF mutations at PLAG27 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signaling. Finally, APOC3 is a gene which retards clearance of plasma triglyceride-rich lipoproteins and where heterozygous deficiency confers protection against coronary heart disease.4,5 In Pakistan, we now observe APOC3 homozygous pLoF carriers; we recalled these knockout humans and challenged with an oral fat load. Compared with wild-type family members, APOC3 knockouts displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a ‘human knockout project’, a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.

High-Density Lipoprotein Subfractions and Cholesterol Efflux Capacity Are Not Affected by Supervised Exercise but Are Associated with Baseline Interleukin-6 in Patients with Peripheral Artery Disease.

To quantify the association between high-density lipoprotein (HDL) subfractions, efflux capacity, and inflammatory markers at baseline and the effect of supervised exercise on these HDL parameters in patients with peripheral artery disease (PAD). The study to improve leg circulation (SILC) was a randomized trial of supervised treadmill exercise, leg resistance training, or control in individuals with PAD. In a post hoc cross-sectional analysis, we quantified the associations between baseline HDL subfraction concentrations (HDL2 and HDL3), HDL-C efflux capacity, and inflammatory markers [C-reactive protein (CRP) and interleukin-6 (IL-6)]. We then examined the effect of supervised exercise on changes in these lipoprotein parameters and inflammatory markers in 88 patients from SILC. Baseline HDL-C efflux capacity was associated with baseline concentrations of HDL2 (β = 0.008, p = 0.0106), HDL3 (β = 0.013, p < 0.0001), and IL-6 (β = -0.019, p = 0.03). Baseline HDL3 concentration was inversely associated with IL-6 concentration (β = -0.99, p = 0.008). Compared to control, changes in HDL2, HDL3, normalized HDL-C efflux capacity, CRP, or IL-6 were not significantly different at 6 months following the structured exercise intervention. HDL efflux and HDL3 were inversely associated with IL-6 in PAD patients. Structured exercise was not associated with changes in HDL subfractions, HDL-C efflux capacity, CRP, and IL-6 in PAD patients. Our preliminary findings support the theory that inflammation may adversely affect HDL structure and function; however, further studies are needed to evaluate these findings.

Determination of proteins in blood. Part 1: Determination of total protein and albumin

The review presents a chronological development of procedures for determining the concentrations of total protein and albumin; total concentration of globulins; concentrations of subfractions, classes, and subclasses of globulins; and total concentrations of globulin subclasses in human blood. A brief overview of these procedures and the results of their comparative tests in medical examination of patients are given. The considered procedures are systematized; their advantages and disadvantages are discussed. It is noted that procedures for measuring the concentration of total protein, albumin, and globulin classes in plasma, serum, and whole blood are widely used in modern clinical diagnostic laboratories when performing routine assays. The concentrations of globulin subclasses and total concentrations of globulin subclasses in blood are mainly determined in biomedical research. Procedures for measuring the concentration of total globulins and globulin subfractions in plasma and serum are of historical importance and now are barely applied in clinical and diagnostic laboratories.

Association of serum lipids and coronary artery disease with polymorphisms in the apolipoprotein AI-CIII-AIV gene cluster.

Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population. We recruited age, sex matched, 200 CAD patients and 200 healthy controls and tested them for fasting levels of serum lipids. We genotyped selected polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. There were no statistically significant association of selected polymorphisms (or their combinations) with CAD even after employing additive, dominant and recessive models. However there was significant association of selected polymorphisms with various lipid traits amongst the control cohort (p < 0.05). Mean levels of high density lipoprotein cholesterol and triglycerides were found to be significantly higher among controls carrying at least one mutant allele at ApoA1-75G > A (p = 0.019) and ApoCIII SstI (p < 0.001) polymorphism respectively. Our study observed that the selected polymorphisms in the ApoAI-CIII-AIV gene cluster although significantly affect various lipid traits but this affect does not seem to translate into association with CAD, at least among North Indian population.

Associations between follicular fluid high density lipoprotein particle components and embryo quality among in vitro fertilization patients.

Follicular redox balance is likely to be important for embryo quality during in vitro fertilization (IVF), and the anti-oxidative high desity lipoprotein (HDL) particle is the sole lipoprotein measured in follicular fluid (FF). Therefore, we investigated FF HDL particle components as predictors of embryo quality during IVF. Two research follicles collected from each participant were individually tracked, and 103 women having at least one developed embryo were included in the analysis. Concentrations of 15 non-cholesterol HDL particle components and 26 HDL-cholesterol (HDL-C) particle size subfractions were determined. Embryo quality was assessed for embryo cell number, embryo fragmentation, and embryo symmetry. Multivariable Poisson regression with a sandwich variance estimator was used to evaluate associations between HDL particle components and embryo quality, adjusted for covariates. Higher γ-tocopherol concentration was associated with less embryo fragmentation (relative risk [RR] = 4.43; 95% confidence interval [CI] 1.78, 11.06), and higher apolipoprotein A-1 concentration was associated with full embryo symmetry (RR = 3.92; 95% CI 1.56, 9.90). Higher concentrations of HDL-C subfractions in the large and medium particle size ranges were associated with poorer embryo quality. FF HDL lipophilic micronutrients and protein components, as well as HDL-C particle size, may be important predictors of embryo quality during IVF.

Prepregnancy Adverse Lipid Profile and Subsequent Risk of Gestational Diabetes.

Lower low-density lipoprotein (LDL) peak diameter and a predominance of small, dense LDL are associated with type 2 diabetes, but it is unclear whether they are a risk factor for gestational diabetes mellitus (GDM). To evaluate whether prepregnancy lipid profile predicts the development of GDM during pregnancy. A nested case-control study among women who participated in a multiphasic health exam, where blood was collected and stored between 1984 and 1996, and who then had a subsequent pregnancy between 1984 and 2009. Kaiser Permanente Northern California. Cases were 254 women who developed GDM. Two controls were selected for each case and matched for year of blood draw, age at baseline, age at pregnancy, and number of intervening pregnancies. Prepregnancy LDL peak diameter and prepregnancy lipid subfraction concentrations grouped according to size, and the odds of developing GDM. Women in the lowest quartiles of LDL peak diameter and high-density lipoprotein had increased odds of GDM compared with women in the highest quartiles (odds ratio [95% CI], 2.60 [1.37-4.94] and 1.98 [1.01-3.86], respectively), in multivariable adjusted models. Being in the highest quartile of small and very small LDL subfractions also increased the odds of GDM (2.61 [1.35-5.03] and 2.44 [1.22-4.85], respectively). Lower LDL peak diameter size and high-density lipoprotein levels and higher levels of small and very small LDL subfraction groups were present years before pregnancy in women who developed GDM. A prepregnancy atherogenic lipid profile may help identify women at risk of GDM to target for prevention.

High-density lipopoprotein antioxidant capacity, subpopulation distribution and paraoxonase-1 activity in patients with systemic lupus erythematosus.

BackgroundThe causes of increased cardiovascular risk in systemic lupus erythematosus (SLE) are not understood thoroughly, although presence of traditional cardiovascular risk factors and disease-specific agents were also proposed. In this study, we investigated the quantitative changes in the lipid profile, as well as qualitative characteristics of high-density lipoprotein (HDL) and markers of inflammation and disease activity in SLE patients.MethodsLipoprotein levels were determined in 51 SLE patients and 49 healthy controls, matched in age and gender. HDL antioxidant capacity was determined spectrophotometrically with a cell-free method of hemin-induced low-density lipoprotein (LDL) oxidation. Polyacrylamide gel-electrophoresis was used for HDL subfraction analysis. Human paraoxonase-1 (PON1) activity, apolipoprotein A1 (ApoA1) and oxidized LDL concentrations, as well as interleukin-6, high-sensitivity C-reactive protein, serum amyloid A and monocyte chemotactic protein-1 levels were determined.ResultsHDL-cholesterol and ApoA1 concentrations decreased significantly in SLE subjects. Also, PON1 arylesterase activity (125.65 ± 26.87 vs. 148.35 ± 39.34 U/L, p = 0.001) and total HDL antioxidant capacity (165.82 ± 58.28 % vs. 217.71 ± 54.36 %, p < 0.001) were significantly reduced in patients compared to controls. Additionally, all HDL subfraction concentrations were significantly decreased in patients, while the levels of the examined inflammatory markers were significantly elevated in SLE subjects. The latter correlated positively with disease activity, and negatively with HDL concentration and total HDL antioxidant capacity, respectively. PON1 arylesterase activity and erythrocyte sedimentation rate were independent predictors of total HDL antioxidant capacity.ConclusionsInduced by the systemic inflammation, altered composition and antioxidant activity may diminish the anti-atherogenic effect of HDL and therefore may contribute to the increased cardiovascular risk of SLE patients.

Effect of short term aerobic exercise on fasting and postprandial lipoprotein subfractions in healthy sedentary men.

BackgroundOur goal was to investigate the effect of short term exercise on fasting and postprandial lipoprotein profile.MethodsHealthy sedentary men exercised 20 min for four days. The intensity of exercise was modulated to maintain 75–80 % of a calculated HRmax. Before and after the exercise program, fasting and postprandial (4 h after standard meal) concentrations of lipoprotein subfractions were measured by an electrophoresis in polyacrylamide gel and total concentrations of TAG, LDL and HDL by enzymatic colorimetric method. After 2 days of rest, fasting and postprandial concentrations of lipoprotein fractions and subfractions were measured to determine a persistency of a changes in the lipoprotein profile.Results4 days of physical exercise led to statistically significant decrease of concentration of triacylglycerol in fasting (76.29 ± 20.07, 53.92 ± 10.90, p < 0.05) and postprandial state (139.06 ± 23.72, 96.55 ± 25.21, p < 0.05) VLDL in fasting (21.88 ± 3.87, 18.00 ± 3.93, p < 0.05) and postprandial state (23.88 ± 3.52, 19.25 ± 3.62, p < 0.05), total cholesterol in fasting (162.26 ± 23.38, 148.91 ± 17.72, p < 0.05) and postprandial state (163.73 ± 23.02, 150.08 ± 18.11, p < 0.05). Atherogenic medium LDL decreased also in fasting (9.89 ± 3.27, 6.22 ± 2.55, p < 0.001) and postprandial state (8.88 ± 6.51, 6.88 ± 5.57, p < 0.001). However decrease of large IDL (25.38 ± 3.54, 23.88 ± 3.91, p < 0.05) and large LDL particles (42.89 ± 11.40, 38.67 ± 9.30) was observed only in postprandial state. Total HDL concentration remained unchanged but we observed statistically significant decrease of small HDL particles in fasting (6.11 ± 2.89, 4.22, p < 0.05) and postprandial state (6.44 ± 3.21, 4.56 ± 1.33, p < 0.05). Concentration of these particles are associated with progression of atherosclerosis. All changes of fasting and postprandial lipoprotein profile disappeared after 2 days of rest.ConclusionJust 4 daily settings of 20 min of physical exercise can lead to significant positive changes of fasting and postprandial lipoprotein profile.

Endogenous Sex Steroid Hormones, Lipid Subfractions, and Ectopic Adiposity in Asian Indians.

Estradiol, testosterone (T), and sex hormone binding globulin (SHBG) levels are associated with lipid subfractions in men and women. Our objective was to determine if associations are independent from adipose tissue area among Asian Indians. We used data from 42 women and 57 Asian Indian men who did not use exogenous steroids or lipid-lowering medications. Lipoprotein subfractions including low-density lipoprotein cholesterol (LDL), very low-density lipoprotein cholesterol (VLDL), and intermediate density lipoprotein (IDL) were assessed by ion mobility spectrometry. Intra-abdominal adiposity was assessed by computed tomography. Multivariable regression models estimated the association between sex hormones with lipoprotein subfractions before and after adjustment for adiposity. Among women, lower logSHBG levels were associated with smaller logLDL particle size and higher logtriglycerides, logVLDL, and logIDL, although these associations were attenuated with adjustment for visceral adiposity in particular. Among women, lower logSHBG levels was significantly associated with lower logmedium LDL and logsmall LDL concentrations even after consideration of visceral and hepatic adiposity and insulin resistance as represented by the homeostasis model assessment of insulin resistance (HOMA-IR). Among men, lower logSHBG was also associated with smaller logLDL peak diameter size and higher logtriglycerides and logVLDL, even after adjustment for HOMA-IR and adiposity. Relationships between sex steroids and lipid subfractions were not significant among women. Among men, higher total testosterone was associated with higher logHDL and logLDL particle size, and lower logtriglycerides and logVLDL, but these associations were partially attenuated with adjustment for adiposity and HOMA-IR. Among Asian Indians, SHBG is associated with more favorable lipid subfraction concentrations, independent of hepatic and visceral fat.

Relationship between plasma phospholipase A2 concentrations and lipoprotein subfractions in patients with stable coronary artery disease

BackgroundBoth increased lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and atherogenic lipoprotein subfractions have been shown to reflect unfavourable cardiovascular risk. However, the correlation between Lp-PLA2 and lipoprotein subfractions in patients with coronary artery disease (CAD) has not been assessed yet. MethodsA total of 324 consecutive subjects who were not treated with lipid-lowering drugs were enrolled (angiographically proven CAD: n=253; non-CAD: n=71). Plasma Lp-PLA2 concentrations were measured using ELISA. The low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were determined by Lipoprint System. ResultsPlasma Lp-PLA2 concentrations were higher in patients with CAD compared with those without CAD (153.61±78.73 vs. 131.41±65.49ng/ml, p=0.028). The univariable correlation analysis revealed that Lp-PLA2 concentrations were positively correlated with the cholesterol concentrations of each LDL subfractions and the intermediate as well as small HDL subfractions, while negatively linked with the LDL particle size and large HDL-cholesterol (HDL-C) concentrations in CAD group. However, no similar results were observed in the non-CAD group. Furthermore, multivariable regression analysis was performed in patients with CAD and showed that plasma Lp-PLA2 concentrations were independently correlated with the cholesterol concentrations of each LDL subfractions [large LDL-cholesterol (LDL-C): β=0.263, p<0.001; intermediate LDL-C: β=0.327, p<0.001; small LDL-C: β=0.135, p=0.033] and small HDL-C (β=0.133, p=0.034). ConclusionLp-PLA2 concentrations were positively associated with all LDL subfractions and small HDL subfraction, suggesting an interaction between Lp-PLA2 and lipoprotein subfraction phenotypes in the status of CAD.

Serum lipid profile in subjects with traumatic spinal cord injury.

Background and AimsFew large studies have examined the relationship between spinal cord injury (SCI) and lipid profile. We studied serum lipid concentrations in subjects with traumatic SCI in relation to the degree of neurological involvement and time since injury, and compared them with values from a reference sample for the Spanish population (DRECE study).Materials and MethodsA retrospective cohort was built from 177 consecutive cases with traumatic SCI admitted to the SCI unit of the Miguel Servet Hospital in Aragon (Spain). Outcome measures (cholesterol, triglycerides, HDL-c and LDL-c levels) were analyzed according to the ASIA Impairment Scale (AIS), neurological level of injury (involvement of all limbs vs. only lower limbs), and time since injury. All analyses were adjusted for age and sex.ResultsCases without preserved motor function (AIS A or B) had lower total and HDL cholesterol than the others (-11.4 [-21.5, -1.4] mg/dL total cholesterol and -5.1 [-8.8, -1.4] mg/dL HDL-c), and cases with all-limb involvement had lower total, HDL, and LDL cholesterol than those with only lower-limb involvement (-14.0 [-24.6, -3.4] mg/dL total cholesterol, -4.1 [-8.0, -0.2] mg/dL HDL-c, and -10.0 [-19.7, -0.3] mg/dL LDL-c) (all p<0.05). No association was found between lipid concentrations and time since injury. Concentrations of lipid subfractions and triglycerides in SCI subjects were lower than in sex- and age-stratified values from the reference sample.ConclusionA high degree of neurological involvement in SCI (anatomically higher lesions and AIS A or B) is associated with lower total cholesterol and HDL-c.

The influence of temperature calibration on the OC–EC results from a dual-optics thermal carbon analyzer

Abstract. Thermal–optical analysis (TOA) is a widely used technique that fractionates carbonaceous aerosol particles into organic and elemental carbon (OC and EC), or carbonate. Thermal sub-fractions of evolved OC and EC are also used for source identification and apportionment; thus, oven temperature accuracy during TOA analysis is essential. Evidence now indicates that the "actual" sample (filter) temperature and the temperature measured by the built-in oven thermocouple (or set-point temperature) can differ by as much as 50 °C. This difference can affect the OC–EC split point selection and consequently the OC and EC fraction and sub-fraction concentrations being reported, depending on the sample composition and in-use TOA method and instrument. The present study systematically investigates the influence of an oven temperature calibration procedure for TOA. A dual-optical carbon analyzer that simultaneously measures transmission and reflectance (TOT and TOR) is used, functioning under the conditions of both the National Institute of Occupational Safety and Health Method 5040 (NIOSH) and Interagency Monitoring of Protected Visual Environment (IMPROVE) protocols. The application of the oven calibration procedure to our dual-optics instrument significantly changed NIOSH 5040 carbon fractions (OC and EC) and the IMPROVE OC fraction. In addition, the well-known OC–EC split difference between NIOSH and IMPROVE methods is even further perturbed following the instrument calibration. Further study is needed to determine if the widespread application of this oven temperature calibration procedure will indeed improve accuracy and our ability to compare among carbonaceous aerosol studies that use TOA.

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate.

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels.

Effect of cascade plasma filtration on spectrum of subfractions of low density lipoproteins in blood plasma of patients with ischemic heart disease

We studied effect of cascade plasma filtration on subfractions of low density lipoproteins (LDL) in 16 patients with ischemic heart disease (IHD) and hyperlipidemias refractory to drug therapy. The procedure caused 37.6 ± 1.4%, 43.1 ± 2.5%, and 50.9 ± 1.4% lowering of total, low density lipoprotein cholesterol, and apolipoprotein B-100, respectively. The use of filters led to removal of larger less atherogenic LDL-1 and LDL-2 subfractions with relative accumulation of small dense LDL-3, LDL-4, and LDL-5 subfractions. Lowering of concentrations of all LDL subfractions was caused by specific LDL apheresis by immunosorbtion in 4 patients with IHD. Removal of small dense LDL was more effective than that of large less atherogenic LDL-1 and LDL-2 subfraction. Thus we found differences in spectrum of LDL removed by cascade plasma filtration and immunosorbtion. The use of filters was associated with less effective removal of most atherogenic small dense LDL than of large LDL particles what led to redistribution of concentrations of various LDL subfractions towards atherogenic profile of lipoproteins. These results could constitute a basis for revision of methods of conduct of cascade plasma filtration procedures in patients with IHD.

Comparison of four methods of analysis of lipoprotein particle subfractions for their association with angiographic progression of coronary artery disease

BackgroundCompare gradient gel electrophoresis (GGE), vertical auto profile ultracentrifugation (VAP-II), nuclear magnetic resonance spectroscopy (NMR), and ion mobility for their ability to relate low- (LDL), intermediate- (IDL), very-low-density (VLDL) and high-density lipoprotein (HDL) subfraction concentrations to atherosclerotic progression. Methods and resultsRegression analyses of 136 patients who received baseline and follow-up coronary angiographies and subfraction measurements by all four methods in the HDL Atherosclerosis Treatment Study. Prior analyses have shown that the intervention primarily affected disease progression in proximal arteries with <30% stenoses at baseline.Three-year increases in percent stenoses were consistently associated with higher on-study plasma concentrations of small, dense LDL as measured by GGE (LDLIIIb, P = 10−6; LDLIVa, P = 0.006; LDLIVb, P = 0.02), VAP-II (LDL4, P = 0.002), NMR (small LDL, P = 0.001), and ion mobility (LDL IIb, P = 0.04; LDLIIIa, P = 0.002; LDLIIIb, P = 0.0007; LDLIVa, P = 0.05). Adjustment for triglycerides, HDL-cholesterol, and LDL-cholesterol failed to eliminate the statistical significance for on-study GGE estimated LDLIIIb (P = 10−5) and LDLIVa (P = 0.04); NMR-estimated small LDL (P = 0.03); or ion mobility estimated large VLDL (P = 0.02), LDLIIIa (P = 0.04) or LDLIIIb (P = 0.02). All methods show that the effects were significantly greater for the on-study than the baseline small, dense LDL concentrations, thus establishing that the values concurrent to the progression of disease were responsible. The rate of disease progression was also related to individual VLDL, IDL, and HDL subclasses to differing extents among the various analytic methods. ConclusionFour methodologies confirm the association of small, dense LDL with greater coronary atherosclerosis progression, and GGE, NMR, and ion mobility confirm that the associations were independent of standard lipid measurements.Clinical Trial Registration: clinicaltrials.gov/ct2/show/NCT00000553.