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Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: a randomized, double-blind, placebo-controlled, multicenter, crossover study.

BACKGROUND: Fenofibrate lowers serum total cholesterol and triglyceride levels while it elevates serum high-density lipoprotein cholesterol (HDL-C) level. OBJECTIVE: The aim of this study was to investigate the effects of fenofibrate on the particle size of high-density lipoprotein (HDL). METHODS: Patients with hyperlipidemia (as defined by serum triglyceride level > or = 150 mg/dL in the fasting state) were enrolled in this randomized, double-blind, placebo-controlled, multicenter, crossover study. Fenofibrate 300 mg (corresponding to 200 mg of micronized fenofibrate) or placebo was administered orally once daily after dinner for 8 weeks, followed by crossover of the 2 drugs for an additional 8 weeks. RESULTS: Fifty hyperlipidemic patients (31 men, 19 women; mean [SD] age, 54.6 [12.7] years) were enrolled. Serum total cholesterol and triglyceride levels were significantly reduced with fenofibrate treatment compared with placebo (9.4% [P = 0.007] and 34.4% [P < 0.001], respectively), whereas HDL-C levels were significantly elevated (by 25.8% [P < 0.001]). Lipoprotein lipase (LPL) activity, LPL protein level, and hepatic triglyceride lipase activity increased by 10.5%, 13.4%, and 11.4%, respectively, with fenofibrate compared with placebo. HDL was classified into 3 groups by particle size: HDL3 <88 A; HDL2a > or = 88 A but <98 A; and HDL2b > or = 98 A. The amount of HDL3 increased significantly with fenofibrate compared with placebo (P < 0.001). Fenofibrate was well tolerated during the study. Abnormal clinical laboratory values were noted in 20 of 48 patients (41.7%), but these events were mild and not clinically significant. CONCLUSION: Taken together, these findings indicate that fenofibrate therapy increased the HDL subfraction with the smallest diameter (HDL3), which is largely responsible for withdrawing cholesterol from peripheral cells.

Adult↗

The effect of particle size on the gelation of tissue conditioners.

Tissue conditioner materials comprise a methacrylate polymer powder, usually poly(ethyl methacrylate) (PEM), and a plasticiser that also contains ethanol. The aim of this study was to investigate the effect of ball milling the PEM on gelation time. PEM was used as received and after ball milling for 2, 4, 8 and 16 h. Particle size was measured in each case and gelation time at 37 degrees C when mixed with butyl phthalyl butyl glycollate (BPBG). Gelation time reduced with increasing milling time of the powder, however it was found that increase in the fines initially had a more significant affect than overall reduction in average particle size. The gelation time of unmilled and 16 h milled PEM were also measured when mixed with BPBG and various levels of ethanol. Unmilled PEM with 4% ethanol had a gelation time of 13.5 +/- 2.0 min compared to 5.5 +/- 1.0 min for the 16h milled PEM which was similar to that for the commercial material, Viscogel (6.0 +/- 1.0 min). Ball milling the PEM reduces the level of ethanol required to produce a clinically acceptable gelation time.

Biocompatible Materials↗

Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease.

Plasma high density lipoproteins (HDL) can be separated into two subpopulations of apolipoprotein A-I-containing particles: those that also contain apoA-II [Lp(AI w AII)] and those that do not [Lp(AI w/o AII)]. These particles were isolated by immunoaffinity chromatography from 17 men (9 normolipidemic (NL), 8 hyperlipidemic (HL) with symptomatic coronary artery disease (CAD), from 17 NL men without any symptoms of CAD (healthy controls), and from 10 NL men with entirely normal coronary arteriograms (CAD-free controls). The distributions of particle size in these two subpopulations were determined by gradient gel electrophoresis and densitometric scanning. Approximately half of the Lp(AI w AII) particles in all subjects were distributed in the 8.2-9.2 nm interval. For patients with CAD, a greater fraction of the particles were small, in the 7.0-8.2 nm interval [33% in CAD vs. 26% in CAD-free controls (P less than 0.01) and 19% in healthy controls (P less than 0.0001)], and a smaller fraction of the particles were in the 9.2-11.2 nm interval (14% in CAD vs. 24% in CAD-free control (P less than 0.002) and healthy control groups (P less than 0.001). The Lp(AI w/o AII) of both control groups were primarily composed of two discrete subpopulations in the 8.2-9.2 nm and the 9.2-11.2 nm intervals. In CAD patients there were fewer particles in the 9.2-11.2 nm size interval (23% in CAD vs. 33% in CAD-free controls (P less than 0.005) and 36% in healthy controls (P less than 0.0001), and more particles in the smallest 7.0-8.2 nm size interval (32% in CAD vs. 23% in CAD-free controls (P less than 0.01) and 18% in healthy controls (P less than 0.001]. Thus, the spectrum of HDL particle sizes in patients with CAD tends to be shifted toward the smaller particle when compared with the two control groups. This was observed in both NL and HL patients with HDL cholesterol (CH) values in the normal range. As a group, CAD patients had lower HDL (42 +/- 7 mg/dl) and HDL2 (6 +/- 4 mg/dl) CH than healthy (HDL: 49 +/- 7, HDL2: 12 +/- 6 mg/dl) and CAD-free (HDL: 51 +/- 9, HDL2: 12 +/- 6 mg/dl) controls. When controls and patients were compared for their frequencies of abnormal HDL CH levels and particle sizes, abnormalities in HDL and HDL2 CH levels were not significantly more frequent (twofold) among CAD patients than among controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Influence of substrate wood-chip particle size on shiitake (Lentinula edodes) yield.

Wood chips from four commercial hardwood sawmills were screened with 10 US standard sieves (4-0.21 mm) to assess particle size distributions. 96-98% of wood chips were < 4 mm while 95-99% of particles were > 0.21 mm. The majority (mean = 64.5%) of wood chips passed through US standard sieve size 14 (< 1.4 mm). Shiitake (Lentinula edodes) was grown in three crops to determine the effect of four particle size classes (1 = 2.8-4 mm; 2 = 1.7-2.8 mm; 3 = 0.85-1.7 mm; 4 = < 0.85 mm) on mushroom yield. Yields from substrates prepared with wood chips from class 4 (< 0.85 mm) were lower by 27.7%, 12.4% and 2% (mean = 14.9%) for Crops I, II, and III, respectively, when compared to controls. Profiling of wood chips may help growers optimize their production media and reduce production costs.

Crops, Agricultural↗

Effects of particle size on the biological availability of calcium and phosphorus in defluorinated phosphate for chicks.

A total of 576 d-old, male, broiler chicks were used in two trials 1) to determine the range of Ca and P levels over which the response in bone characteristics is linear and 2) to determine the influence of particle size of defluorinated rock phosphate (DFP) on the bioavailability of Ca and P in DFP. Six treatments were used in Experiment 1 in which varying percentages of added Ca (.00, .06, .12, .24, .36, and .48%) and added P (.00, .05, .10, .20, .30, and .40%) were evaluated in a corn-soybean meal diet containing 23% CP, .47% Ca, and .39% P (.14% available P). Weight gain, feed intake, and tibia breaking strength increased (P less than .001) with increasing levels of dietary Ca and P. Treatments in Experiment 2 consisted of: 1) Diet 1, a corn-soybean meal basal diet (23% CP, .50% Ca, .46% P, .21% available P), 2) Diet 1 with .12% added Ca from calcium carbonate (CC) and .07% added P from monosodium phosphate (MSP), 3) Diet 1 with .24% added Ca from CC and .14% added P from MSP; and 4 to 8), Diet 1 with .24% added Ca and .14% added P from five particle sizes of DFP. Feed intake, weight gain, and tibia breaking strength and ash percentage increased linearly (P less than .01) and feed:gain ratio decreased quadratically (P less than .10) with increasing percentages of added Ca and P in Diets 1 to 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dietary fibre fermentation in the rat intestinal tract: effect of adaptation period, protein and fibre levels, and particle size.

1. The fermentative breakdown of one resistant type of dietary fibre (wheat bran) and one easily-fermented fibre (low-methoxyl pectin) was studied with respect to the length of the adaptation period and fibre level in the diet. The breakdown of the resistant fibre was also studied regarding the protein level in the diet and particle size of the fibre. 2. Prolongation of the adaptation period from 4 to 18 d decreased the faecal dry weight considerably. The excretion of dietary fibre however, was similar, whereas a decrease in faecal nitrogen excretion could be seen. 3. A level of dietary protein of less than 50 g/kg impaired the fermentation of wheat-bran fibre, whereas a level higher than 100 g protein/kg did not further increase the degree of fermentation of the fibre. 4. The particle size did not change the fermentability of the fibre, equal amounts of the main components of coarse and milled bran being excreted in faeces. 5. Two different levels of wheat-bran fibre (48 and 96 g/kg) in the diet did not influence the fibre breakdown. Similar results were obtained with two levels of fibre from low-methoxyl pectin (42 and 84 g/kg), but a tendency towards a decreased percentage of faecal excretion of uronic acids was seen at the lower level of low-methoxyl pectin.

Adaptation, Physiological↗

Particle size distributions of polycyclic aromatic hydrocarbons in rural and urban atmosphere of Tianjin, China.

The size distributions of 16 polycyclic aromatic hydrocarbons (PAHs) and particle mass less than 10 microm in aerodynamic diameter (Dp) were measured using a nine-stage low-volume cascade impactor at rural and urban sites in Tianjin, China in the winter of 2003-2004. The particles exhibited the trimodal distribution with the major peaks occurring at 0.43-2.1 and 9.0-10.0 microm for both urban and rural sites. The concentrations of the total PAH (sum of 16 PAH compound) at rural site were generally less than those of urban site. Mean fraction of 76.5% and 63.9% of the total PAH were associated with particles of 0.43-2.1 microm at rural and urban sites, respectively. Precipitation, temperature, wind speed and direction were the important meteorological factors influencing the concentration of PAHs in rural and urban sites. The distributions of PAHs concentration with respect to particle size were similar for rural and urban samples. The PAHs concentrations at the height of 40 m were higher than both of 20 and 60 m at urban site, but the mass median diameter (MMD) of total PAH increased with the increasing height. The mid-high molecular weight (278 >or= MW >or= 202) PAHs were mainly associated with fine particles (Dp or=MW >or=178) PAHs were distributed in both of fine and coarse particle. The fraction of PAHs associated with coarse particles (Dp>2.1 microm) decreased with increasing molecular weight. The relatively consistent distribution of PAHs seemed to indicate the similar combustion source of PAHs at both of rural and urban sites. The fine differences of concentration and distribution of PAHs at different levels at urban site suggested that the different source and transportation path of particulate PAHs.

Air↗

Genetic variation at the scavenger receptor class B type I gene locus determines plasma lipoprotein concentrations and particle size and interacts with type 2 diabetes: the framingham study.

The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transport pathway. We have previously reported three common polymorphisms associated with plasma lipids and body mass index. We hypothesized that diabetic status may interact with these polymorphisms in determining plasma lipid concentrations and particle size. We evaluated this hypothesis in 2463 nondiabetic (49% men) and 187 diabetic (64% men) participants in the Framingham Study. SR-BI and APOE genotypes, anthropometric, clinical, biochemical, and lifestyle variables were determined. After multivariate adjustment, we found a consistent association between the exon 8 polymorphism and high-density lipoprotein cholesterol concentration and particle size. Interaction effects were not significant for exon 8 and intron 5 polymorphisms. However, we found statistically significant interactions between SR-BI exon 1 genotypes and type 2 diabetes, indicating that diabetic subjects with the less common allele (allele A) have lower lipid concentrations. For low-density lipoprotein cholesterol, the adjusted means (+/-SE) were 3.31 +/- 0.03 and 3.29 +/- 0.04 mmol/liter for G/G and G/A or A/A in nondiabetics, respectively, compared with 3.19 +/- 0.10 and 2.75 +/- 0.01 mmol/liter for G/G and G/A or A/A in diabetics (P = 0.03 for interaction). Similar results were obtained for HDL(2)-C. In conclusion, SR-BI gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects.

Alleles↗

Capillary zone electrophoresis of sub-microm-sized particles in electrolyte solutions of various ionic strengths: size-dependent electrophoretic migration and separation efficiency.

To gain insight into the mechanisms of size-dependent separation of microparticles in capillary zone electrophoresis (CZE), sulfated polystyrene latex microspheres of 139, 189, 268, and 381 nm radius were subjected to CZE in Tris-borate buffers of various ionic strengths ranging from 0.0003 to 0.005, at electric field strengths of 100-500 V cm(-1). Size-dependent electrophoretic migration of polystyrene particles in CZE was shown to be an explicit function of kappaR, where kappa(-1) and rare the thickness of electric double layer (which can be derived from the ionic strength of the buffer) and particle radius, respectively. Particle mobility depends on kappaR in a manner consistent with that expected from the Overbeek-Booth electrokinetic theory, though a charged hairy layer on the surface of polystyrene latex particles complicates the quantitative prediction and optimization of size-dependent separation of such particles in CZE. However, the Overbeek-Booth theory remains a useful general guide for size-dependent separation of microparticles in CZE. In accordance with it, it could be shown that, for a given pair of polystyrene particles of different sizes, there exists an ionic strength which provides the optimal separation selectivity. Peak spreading was promoted by both an increasing electric field strength and a decreasing ionic strength. When the capillary is efficiently thermostated, the electrophoretic heterogeneity of polystyrene microspheres appears to be the major contributor to peak spreading. Yet, at both elevated electric field strengths (500 V/cm) and the highest ionic strength used (0.005), thermal effects in a capillary appear to contribute significantly to peak spreading or can even dominate it.

Electrolytes↗

Association of apolipoprotein A5 variants with LDL particle size and triglyceride in Japanese Americans.

A new apolipoprotein (apo) gene, APOA5, was recently identified on chromosome 11q23, and common variants in the gene have been associated with plasma triglyceride (TG) levels in several studies. The purpose of the present study was to examine the association of five single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene with low-density lipoprotein (LDL) particle size using a community-based sample of Japanese American families, including examining whether the associations with LDL size are independent of, or primarily reflecting, TG levels. Genetic association analyses were performed using 154 unrelated individuals, quantitative transmission disequilibrium tests (TDT) in 238 nuclear families, a sample of 24 hypertriglyceridemic subjects with matched, normotriglyceridemic controls, and using haplotype analyses. There was a high degree of allelic association between several of the SNPs, with complete linkage disequilibrium (LD) between -1131C>T and the -3A>G SNP which alters a potential Kozak sequence. All approaches demonstrated associations between the -3A>G APOA5 variant and both decreased LDL size and increased TG levels. The frequency of the rare allele was higher than reported for Caucasian, Hispanic, and African Americans, but similar to that in Japan and China. Therefore, the haplotype containing the -1131C and -3G variants, and possibly specifically the -3A>G SNP in APOA5, may be a major genetic determinant of LDL particle size and TG levels among ethnic Asians.

Alleles↗

[Soil particle size fractionation with centrifugation method].

According to the rotor size of Mandal RC5C and Stoks' law, a segregation procedure for soil particle size fractionation was designed, and used for the particle separation of Huangmian soil(Calcaric cambisols, FAO), Huihe soil (Haplic greyxems, FAO), and Helu soil(Calcic kastanozems, FAO) in the Loess Plateau of China, and of Orthic Brown Chernozem, and Orthic Black Chernozem in Canadian Prairie. The fractionation results of the 5 soils by using this procedure were in line with those of the standard pipette method.

Centrifugation↗

Enantioseparations using nonaqueous capillary electrochromatography on cellulose and amylose tris(3,5-dimethylphenylcarbamates) coated on silica gels of various pore and particle size.

Enantioseparations of chiral compounds were studied in nonaqueous capillary electrochromatography (NAQ CEC) with cellulose and amylose tris(3,5-dimethylphenylcarbamates) (Chiralcel OD and Chiralpak AD, respectively) coated on the silica gels of various pore and particle size. Increasing intraparticle perfusive transport with increasing pore size of silica favorably affected peak efficiency and resolution of enantiomers, although some decrease of separation factor was observed in the pore size range 60-200 A. Further improvement of peak efficiency was observed when the particle size of silica was reduced from 5 to 3 microm. The effects of a separation medium and temperature are also reported and the data obtained in the same capillaries in CEC and capillary liquid chromatography (LC) mode are compared.

Amylose↗

Optimal bulking agent particle size and usage for heat retention and disinfection in domestic wastewater sludge composting.

Composting of two types of sludge produced in wastewater treatment plants, raw sludge (RS) and anaerobically digested sludge (ADS), has been systematically studied by means of the experimental design technique. The results have been analyzed using a full factorial experimental design in order to determine the optimal conditions for composting such sludges in terms of bulking agent particle size and bulking agent:sludge volumetric ratio, two of the key parameters to ensure an optimal performance of the composting process. The objective function selected was a simulated death kinetics of Salmonella, which was chosen as a model pathogen microorganism to represent the disinfection of the material. For both types of sludge, optimal values were found at 5mm bulking agent particle size and 1:1 bulking agent:sludge volumetric ratio when a Gaussian function was fitted to the experimental data. Pilot scale experiments using optimal values obtained were successfully undertaken and confirmed a full disinfection of the sludge by means of the composting process. A mathematical model to simulate the disinfection performance of a composting material is presented. The model can be applied to simulate the disinfection performance of a given pathogen.

Disinfection↗

Correlations of plasma lipoproteins with LDL subfractions by particle size in men and women.

Nondenaturing gradient gel electrophoresis of plasma low density lipoprotein (LDL) has been used to identify major LDL subclasses that are influenced by genetic and other factors. In the present paper, this technique has been extended by measuring absorbance of lipid- or protein-stained gels as an index of concentration at intervals of 0.05 nm across the entire LDL particle size range (21.8-30 nm) in moderately overweight men (n = 115) and women (n = 78). When LDL absorbance levels were correlated with other lipoprotein variables, we found that the strengths of the correlations with each of triglycerides, apolipoprotein (apo) B, high density lipoprotein (HDL)2, and apoA-I achieve relative maximum values for two regions within the small LDL range (21-26 nm), one within LDL-IVB (22-23.2 nm) and a second within LDL-III (24.2-25.5 nm). We also found that the increase in LDL accompanying higher triglyceride levels occurs below 25.5 nm in men and between 24.5 and 26.5 nm in women, suggesting either that triglycerides are related to different LDL subclasses in men and women, or that particle sizes of metabolically homologous LDL subclasses may differ in men and women. As compared to analytic ultracentrifuge measurements, gradient gel measurements of LDL absorbance by the procedure described here provide greater resolution of LDL subclasses but less precision in estimating LDL levels.

Adult↗

Raw soybeans and roasted soybeans of different particle sizes. 2. Fatty acid utilization by lactating cows.

This study was conducted to examine the effects of feeding whole raw soybeans and roasted soybeans of different particle sizes on utilization by ruminal bacteria and lactating cows. Five cows with ruminal and duodenal cannulas were used in a 5 x 5 Latin square design. Diets contained 55% corn silage and 45% concentrate. Treatments were control (Ca soaps at 4.24% of dietary DM), whole raw soybeans, whole roasted soybeans, cracked roasted soybeans, or ground roasted soybeans. All soybean diets contained 19.7% soybeans. Source of fat (Ca soaps vs. soybeans) caused more differences in utilization of fatty acids than did processing of soybeans. Ruminal bacteria harvested from cows fed roasted soybeans had higher fatty acid content than from cows fed raw soybeans. Different methods for calculation of ruminal biohydrogenation of fatty acids are discussed. Roasting tended to increase the total tract digestibility of fatty acids, and roasted soybeans tended to increase polyunsaturated fatty acids in milk compared with raw soybeans, primarily because of changes in concentration of C18:2. Change in particle size of roasted soybeans had minor effects on utilization of fatty acids. Decisions on processing of soybeans need to be based primarily on factors other than fatty acid digestibility.

Animals↗

Comparison between direct methods for determination of microbial cell volume: electron microscopy and electronic particle sizing.

Size frequency distributions of different phototrophic and heterotrophic microorganisms were determined by means of scanning and transmission electron microscopy and electronic particle sizing. Statistically significant differences existed among the three techniques used in this study. Cells processed for electron microscopy showed lower mean cellular volumes than those processed for electronic particle sizing, reflecting a shrinkage by factors ranging from 1.1 to 6.2 (mean, 2.3). Processing of cells for scanning electron microscopy caused higher shrinkage than processing for transmission electron microscopy. Shrinkage was dependent neither on the size nor on the cell wall type of the microorganism. When processed for scanning electron microscopy, phototrophic bacteria were strongly shrunken, whereas heterotrophic microorganisms were less affected. A direct relationship existed among phototrophic bacteria between percentage of shrinkage and specific pigment content. This was probably a consequence of the pigment extraction by organic solvents during the dehydration process, previous to the critical point drying, necessary to examine the specimens under the scanning electron microscope.

Bacteria↗

Comparison of output particle size distributions from pressurized aerosols formulated as solutions or suspensions.

The delivery of particles as small as possible (preferably less than 5 microns) to the respiratory tract should be the aim of those formulating metered dose inhalers (MDIs). This may be facilitated by the formulation of solution, rather than suspension-type, pressurized aerosol units. Two series of MDIs were compared; one contained suspended micronized disodium fluorescein (0.1%, w/v), while the other contained the same concentration of dissolved salicylic acid. Either oleic acid, L-alpha-phosphatidylcholine, or sorbitan trioleate was incorporated at 0.15% (w/v) as suspending agent (disodium fluorescein) or solubilizing agent (salicylic acid). The propellant blend was 70% (w/w) Freon 12 and 30% (w/w) Freon 11 in all cases. This exhibited a vapor pressure of 50.6 psig (444.7 kPa) at 21 degrees C. The output particle size distribution of the aerosol reaching the cascade impactor showed a mass median aerodynamic diameter (MMAD) of approximately 4 and 2 microns for the suspension and solution formulations respectively, regardless of the surfactant used. Larger MMADs were observed for solution aerosols formulated with oleic acid (2.32 microns) compared to those containing L-alpha-phosphatidylcholine (1.93 microns) or sorbitan trioleate (2.07 microns). Possible reasons for these observations are discussed.

Aerosols↗

Radon emanation from coals: effects of moisture and particle size.

The emanation of 222Rn from several coal samples (including lignites) was measured as a function of particle size and water content. From 10 to 0.85 mm, particle diameter had no measurable effect on 222Rn emanation. However, the fraction of 222Rn emanated did have a linear dependence on water content, the upper limit observed being equal to the weight fraction of water in the coal. Coals and lignites having typical concentrations of 238U emanate no more 222Rn than do comparable masses of typical soils. Our results appear to have implications for the spatial relationship between the 226Ra atoms and the pores in the coals on the scale of the 222Rn recoil range (0.05 micron).

Air Pollutants↗