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High density lipoprotein particle size distribution in subjects with obstructive jaundice.

High density lipoproteins (HDL) from 14 patients with obstructive jaundice were examined by gradient gel electrophoresis to determine the effect of obstruction on particle size distribution. HDL from 7 of these patients were fractionated by gel permeation chromatography and further characterized by electron microscopy, SDS gel electrophoresis, apolipoprotein A-I and apolipoprotein A-II immunoturbidimetry, and analysis of chemical composition. In addition, lecithin:cholesterol acyltransferase (LCAT) activity was measured and correlated with plasma apolipoprotein A-I concentration and particle size distribution. HDL were abnormal in all patients regardless of severity, cause, or duration of obstruction. The major HDL subfraction in normal subjects, HDL3a (radius 4.1-4.3 nm) was either absent or considerably diminished, and HDL2b (radius 5.3 nm) was also frequently absent. Very small particles comparable in size to normal HDL3c (radius 3.8 nm) were prominent. In patients with a bilirubin concentration greater than 250 mumol/l, normal HDL had totally disappeared and were replaced by large discoidal particles of radius 8.5 nm and small spherical particles of radius 3.6-3.7 nm. Both populations of particles were markedly depleted of cholesteryl ester and enriched in free cholesterol and phospholipid. The discoidal particles were rich in apolipoproteins E, A-I, A-II, and C, while the small spherical particles contained predominantly apolipoprotein A-I. LCAT activity was diminished in all subjects to 8-54% of normal, and was strongly positively correlated (r = 0.91 P less than 0.05) with plasma apolipoprotein A-I levels.

Adult↗

[The new atherogenic plasma index reflects the triglyceride and HDL-cholesterol ratio, the lipoprotein particle size and the cholesterol esterification rate: changes during lipanor therapy].

The new atherogenic plasma index (AIP) is a logarithmic transformation of the ratio of the molar triglyceride (TG) concentration and high density lipoprotein cholesterol (HDL-C). AIP correlates closely with the size of LDL particles (r = 0.8) and esterification rate of plasma cholesterol devoid of apo B lipoproteins (FERHDL), r = 0.9 which are considered at present the most sensitive indicators of the atherogenic plasma profile. AIP was recommended by the authors, based on analysis of results of 11 previous studies (1156 subjects) where FERHDL and plasma lipid parameters were investigated in different groups of people who differed as to the atherogenic risk. The AIP index was moreover used for evaluation of a clinical study comprising 609 patients with hyperlipidaemia, who were treated for three months with ciprofibrate (Lipanor). The mean AIP values of non-risk groups (plasma from umbilical blood, children, healthy women etc.) equalled zero or were lower, while with an increasing atherogenic risk (men, women after the menopause) AIP reached positive values, incl. high positive values in risk groups (plasma of diabetic subjects, patients with HLP, patients with positive angiography, myocardial infarction etc.). In all groups women had lower AIP values as compared with males. In patients after Lipanor therapy the AIP declined (from 0.58 +/- 0.17 to 0.33_0.18 in men, from 0.50 +/- 0.18 to 0.21 +/- 0.19 in women). If we consider AIP values from negative ones to 0.15 as "safe" from the aspect of atherogenicity, before Lipanor treatment these "safe" levels were recorded in 1.5% men and in 5.2% women and after treatment in 32% men and 48% women. The results indicate, that AIP which reflects the plasma lipoprotein profile quantifies the relations between TG and HDL-C and thus can be an objective indicator of the atherogenic risk and effectiveness of treatment and it is useful because it can be assessed in any surgery.

Adult↗

Particle size and composition related to adverse health effects in aged, sensitive rats.

Small increases in concentrations of ambient particulate matter (PM*) have been linked to adverse health effects, especially in older people and people with preexisting respiratory disease. Some epidemiologic studies have shown the association to be stronger with PM less than 2.5 microm in aerodynamic diameter (PM2.5) than with PM less than 10 microm in aerodynamic diameter (PM10). Some scientists and regulators suggest that 2.5 microm might be an arbitrary cutoff and that the effects might be more pronounced for PM less than 0.1 microm in aerodynamic diameter (ultrafine PM). Our first aim was to determine the relation between size of respirable particles and particle toxicity, as well as the health effects of short-term increases (spikes) in particle concentration against backgrounds of relatively low or high baseline exposures. Our second aim was to determine the effect of spikes in concentration of fine particles (0.7 microm in mass median aerodynamic diameter [MMAD]) and ultrafine particles (35 nm in count median diameter [CMD]) of disparate composition: vanadium pentoxide (V2O5) and carbon black. The relative toxicity of these particles was determined in aged rats with mild pulmonary inflammation induced by instilled endotoxin. Our third aim was to determine the influence of age (aged vs young adult) on particle-induced toxicity in these rats.

Age Factors↗

The influence of the incorporation of cholesterol and water on the particle size, bilayer thickness, melting behavior, and relative sucrose ester composition of reversed vesicles.

The influence of the incorporation of cholesterol and water on the particle size, bilayer thickness, melting behavior, and relative sucrose ester composition of reversed vesicles was studied. Reversed vesicles (RVs) were prepared of sucrose ester in silicon oil by sonication. The RVs were characterized by polarized light microscopy, laser diffraction, high-performance liquid chromatography, small angle X-ray scattering (SAXS), and differential scanning calorimetry. The particle size distributions of the studied dispersions were bimodal with peaks at 5 and 0.4 microm. There was no significant difference in the sucrose ester composition of these two size categories of RVs. The incorporation of cholesterol and water had no effect on the size distribution of the RVs. The SAXS results showed that the RVs prepared without cholesterol and water consisted of bilayers with fully interdigitated alkyl chains. The incorporation of high concentrations of cholesterol caused a phase separation within the bilayers. The incorporation of water also resulted in a phase separation within the bilayers but at a lower cholesterol concentration. The presence of two different size classes of RVs in one RVs dispersion and the phase separation within the bilayers of certain compositions can have consequences for the application of RVs.

Cholesterol↗

Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size: the Framingham Heart Study.

BACKGROUND: Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. METHODS AND RESULTS: We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms -1131T>C and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene-diet interactions between the -1131T>C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (P<0.001) in determining fasting TGs, RLP concentrations, and particle size, but these interactions were not found for the 56C>G polymorphism. The -1131C allele was associated with higher fasting TGs and RLP concentrations (P<0.01) in only the subjects consuming a high-PUFA diet (>6% of total energy). No heterogeneity by sex was found. These interactions showed a dose-response effect when PUFA intake was considered as a continuous variable (P<0.01). Similar interactions were found for the sizes of VLDL and LDL particles. Only in carriers of the -1131C allele did the size of these particles increase (VLDL) or decrease (LDL) as PUFA intake increased (P<0.01). We further analyzed the effects of n-6 and n-3 fatty acids and found that the PUFA-APOA5 interactions were specific for dietary n-6 fatty acids. CONCLUSIONS: Higher n-6 (but not n-3) PUFA intake increased fasting TGs, RLP concentrations, and VLDL size and decreased LDL size in APOA5 -1131C carriers, suggesting that n-6 PUFA-rich diets are related to a more atherogenic lipid profile in these subjects.

Adult↗

Spectroscopic approach for on-line monitoring of particle size during the processing of pharmaceutical nanoparticles.

A novel application of near-infrared (near-IR) spectroscopy for the on-line determination of nanoparticle size of a drug compound in a high solids dispersion is described. The on-line spectroscopic technique provides real-time data for process monitoring and control and overcomes the limitations that are encountered using laboratory-based instrumentation for nanoparticle size determination. Near-IR spectroscopy is capable of providing an accuracy of 2.4 nm near the endpoint of particle production, where the volume-weighted D90 particle size is determined to be 200-220 nm. The accuracy is adequate for endpoint control, which minimizes excess processing and provides control over the particle size throughout nanoparticle production.

Drug Compounding↗

Spatial variations in selected metal contents and particle size distribution in an urban and rural atmosphere of Islamabad, Pakistan.

Spatial variations in total suspended particulate matter (TSP) were investigated for distribution of metals and particle size fractions in the urban and rural atmosphere of Islamabad, Pakistan. The metals Na, K, Fe, Mn, Pb, Cd, Cr, Zn, Ni and Co, and the particle fractions <2.5, 2.5-10, 10-100 and >100 microm were included in the study. TSP samples were trapped on glass fibre filters using high volume samplers and quantification of metals was done using Atomic Absorption Spectrometry employing HNO(3) based wet digestion. At the urban site, Na was dominant at 2.384 microg/m(3) followed by K, Fe and Zn with 0.778, 0.667 and 0.567 microg/m(3) as mean concentrations, respectively. The metal levels for the rural site ranged from 0.002 microg/m(3) for Cd to 1.077 microg/m(3) for Na. However, compared with the urban site, mean Pb concentration showed an almost two-fold enhancement, i.e., 0.163 Vs. 0.327 microg/m(3). Metals and particle size source identification was done using Principal Component Analysis and Cluster Analysis. Five sources were traced out for the urban site: industrial, soil, automobile emissions, metallurgical industries and excavation activities. For the rural site, four sources were recorded: agricultural, automotive emissions, excavation activities and metallurgical units. Collectively, for both the sites, PM(10-100) emerged as a major contributor to TSP, followed by PM(2.5-10), PM(<2.5) and PM(>100) in that order. The metals showed in general positive relationship with fine particulate fractions (PM(2.5-10), PM(<2.5)), and negative correlation with coarse fractions (PM(10-100), PM(>100)). Comparison with the corresponding data from various Asian sites revealed that the levels of Na, K, Fe, Mn, Co and Ni for the present study were lower than those reported for grossly polluted cities of the world.

Agriculture↗

The effect of heat treatment and particle size of bran on mineral absorption in rats.

The effect of heat treatment of bran on the true zinc absorption was measured using an isotope-dilution technique. A bran-based breakfast cereal (heated to 204 degrees for 40 min during manufacture) was incorporated into a semi-synthetic diet at a level of 180 g/kg. A parallel diet was formulated containing an identical weight of untreated bran from the same source plus other ingredients used to make the cereal. 2. Young male Wistar rats (mean weight 80 g) were injected intramuscularly with 65Zn to label body Zn. They were given the heat-treated- and untreated-bran diets for 9 d. During the last 6 d of this period Zn intakes and faecal and urinary Zn were measured in order to calculate apparent Zn retention. True Zn retention was measured by taking into account losses of Zn of endogenous origin (labelled with 65Zn), by measuring faecal and urinary radioactivity of endogenous origin. 3. Heat treatment of bran removed approximately one-third of the phytate, but this was not enough to improve Zn absorption from the diet. True Zn retention measured by isotope dilution was significantly higher (P less than 0.02) than apparent Zn retention measured by the conventional balance technique. 4. The hypothesis that a reduction in particle size of bran would improve mineral availability was tested by feeding coarse and milled bran (100 mg/kg diet) in a semi-synthetic diet to rats and measuring true Fe and apparent Zn absorptions. The importance of phytate was also investigated by feeding a diet containing dephytinized bran. 5. Male Wistar rats (mean weight 172 g) were given diets containing coarse, milled or dephytinized bran for 9 d. Fe and Zn intakes were measured and faeces and urine collected for Fe and Zn analysis. 6. Rhe mean (+/- SE) particle size of the bran was reduced on milling from 3.5 (+/- 1.8) to 0.2-0.5 mm. There were no differences in the fraction of Fe retained between the three groups. Particle size had a small effect on Zn retention which was marginally higher in rats on the milled-bran diet (0.126 (+/- 0.023)) than in those on the coarse-bran diet (0.087 (+/- 0.012)). Total removal of phytate had a greater effect and apparent Zn retention from the dephytinized-bran diet was significantly higher (0.182 (+/- 0.027), P less than 0.001).

Animals↗

The effects of polymorphism, particle size and compression pressure on the dissolution rate of phenylbutazone tablets.

The dissolution rate of phenylbutazone from tablets after disintegration has been used to determine whether the drug particles underwent crushing or bonding during compression. Two polymorphic forms of the drug were used and the predominant effect for high drug concentration (60%), during compression was dependent upon the original particle size of the drug and its polymorphic form. With a low drug concentration (10%) in the tablet, the diluent protected the drug particles from bonding together. The particle size change of the drug during compression was affected by the nature of the diluent present. Lactose had an abrasive action on Form A phenylbutazone compared with Avicel but had little effect on the more ductile Form B. When the contact time of compression was decreased from 29 to 0.26 s, the 6 microns particles of drug showed less bonding at the shorter time (faster rate of compression) but the effect observed with the larger particles was independent the compression rate.

Crystallization↗

A freeze-capture method for the study of platelet-sized particle distributions.

A rapid freezing method was developed to study the distributions of fluorescent platelet-sized particles in flows of blood suspensions through thin-walled capillary tubes. Segments of frozen tubes were mounted in a refrigerated microtome on the stage of an epifluorescence microscope. Sections of tube were cut away, images of newly exposed cross-sections were recorded on video tape, and distances of the particles from the wall were measured from recorded images. The distance data were used to construct histograms that were proportional to the local concentration. Results indicated that this method is suitable for the study of the distribution of platelet-sized particles over a wide range of hematocrit, that the basic profile is reproducible to within 15%, and that the non-uniform profile is not a result of events at the tube entrance.

Blood Platelets↗

Comparison of the effects of atorvastatin or fenofibrate on nonlipid biochemical risk factors and the LDL particle size in subjects with combined hyperlipidemia.

BACKGROUND: Combined hyperlipidemia (CH) is an increasingly prevalent risk factor for premature heart disease, and its treatment is troublesome. The aim of this study was to compare the effects of atorvastatin and fenofibrate on nonlipid biochemical risk factors and the low-density lipoprotein (LDL) particle size in subjects with CH. METHODS: Twenty-nine middle-aged men with CH were randomly assigned to open-label therapy with atorvastatin (10 mg daily) or micronized fenofibrate (200 mg daily); they were sequentially treated with both drugs, with crossover of medication after 10 weeks. RESULTS: Atorvastatin was more efficient in the reduction of total cholesterol, whereas fenofibrate was more efficient in the reduction of triglycerides. Only atorvastatin led to a significant reduction of LDL cholesterol and apolipoprotein B. Only fenofibrate increased high-density lipoprotein cholesterol. Neither drug influenced lipoprotein(a). Mean LDL particle size increased both after fenofibrate (3.08%) and atorvastatin (1.77%). Fenofibrate increased serum homocysteine (HCY) by 36.5%. Atorvastatin had no effect on HCY. Only atorvastatin increased fibrinogen by 17.4%. Only fenofibrate reduced C-reactive protein by 51.7%. Neither drug influenced HOMA (homeostasis model assessment) index of insulin resistance. The plasma level of thiobarbituric acid reactive substances, an index of oxidative stress, decreased after both treatments. CONCLUSIONS: Both atorvastatin and fenofibrate had similar beneficial effects on LDL particle size and on oxidative stress. The effects of both drugs on other parameters such as triglycerides, total and high-density lipoprotein cholesterol, fibrinogen, or HCY differed significantly. These differences, together with the risk profile of a patient, should be considered during selection of a particular lipid-lowering modality.

Apolipoproteins B↗

Laser diffraction estimation of particle size distribution of slightly water-soluble drugs coexisting with additives: application to solid dosage forms.

A simple and quantitative evaluation method for particle size distribution (fx(r)) of slightly water-soluble drugs dispersed in an aqueous medium together with other water-insoluble additives was developed using a laser diffraction method. The particle size distribution function of the powder mixture, (f(r)), was assumed as f(r) = phi x.fx(r) + phi a.fa(r), where phi is the volume fraction of each component dispersed in a measurement medium and fa(r) is the distribution function of another water-insoluble additive "a". In order to calculate fx(r) from f(r), it is necessary to know the density of drug and additive in the measurement medium, d(x) and d(a), but this is difficult to determine since particles usually swell in the medium. Thus, a method was developed to use their relative value, delta a (= da/dx). As a practical application, oxolinic acids (OA) of three sizes (OA-S (about 2 microns), OA-M (about 7 microns) and OA-L (about 24 microns)) were used as model drugs. delta a values were determined for various additives using the mixture of OA-S and each additive. Then, using delta as, fx(r) of OA-M or OA-L in the mixture containing OA-M or OA-L and additives was calculated from the f(r) experimentally determined for the mixture. They agreed well with their original distributions. The method was applied to some dosage forms, and the results obtained had good correlation with those from turbidity, wet sieving or dissolution test.

Algorithms↗

Low-substituted hydroxypropylcellulose as a sustained-drug release matrix base or disintegrant depending on its particle size and loading in formulation.

Tablets of acetaminophen as a model drug were prepared with low-substituted hydroxypropylcellulose (L-HPC) of various particle sizes at various loadings in the formulation. Drug release into an aqueous dissolution medium (pH 1.2) was remarkably sustained from tablets prepared with fine L-HPC (LH41) at loadings of more than 20%. Tablets prepared with less than 20% LH41 or with coarse L-HPCs (LH11, LH21, and LH31) disintegrated in the medium, resulting in rapid release of the drug. The difference in behavior could not be explained in terms of differences in tablet strength, but in swelling and water uptake abilities of the tablet's polymer. Swelling work (swelling force), water penetration speed, and water uptake of LH41 (4.4-microns average particle size) were much smaller than those of coarse L-HPCs. The formation of a continuous gel-like layer on the surface of tablets containing more than 20% LH41 was another factor to sustain the drug release rate.

Acetaminophen↗

Optical particle sizing in backscatter.

Several possibilities for the use of elastic light scattering in the backscatter range (scattering angle theta(s) > 140 deg) for determination of size, velocity, and refractive index of spherical particles are investigated. First the phase Doppler technique is considered. Numerical simulations of light scattering with the Lorenz-Mie theory are used to show that the phase Doppler technique is unsuitable for such backscatter configurations, except for special measurement conditions. The time-shift (or pulse-displacement) technique is then considered by use of the Fourier-Lorenz-Mie theory. Simulations show that up to four fractional signals can be obtained by use of the technique in backscatter, corresponding to the scattering order or modes: surface wave (long path), reflection, second-order refraction (inner path), and a mixture of second-order refraction (outer path) and surface wave (short path). Signal characteristics as a function of particle size, refractive index, and particle ellipticity are studied. Suggestions for a practical measurement instrument are put forward.

Journal Article↗

Particle size and density distributions of two dense matrices in an expanded bed system.

The size and density distributions of two commercial media, that is, Streamline particles and 6% agarose coated steel beads (6AS), in an expanded bed system has been studied with a glass column (26 mm I.D.) modified by side ports. The Streamline particles have a broad size distribution but a relatively uniform density, while the 6AS beads have both broad size and density distributions. The effect of liquid-phase flow velocity, liquid viscosity and settled bed height on the particle size and density distributions is investigated. It is found that the radial mean particle size and density of the two matrices are uniform, while axial classifications are obvious in the expanded beds. For the Streamline, the volume-weighted mean particle size decreases linearly with increasing expanded bed height. For the 6AS beads, however, the mean particle size is even in the axial direction, but the particle density decreases exponentially with the increase of bed height. Moreover, the mean particle size of the Streamline or the density of the 6AS beads is well expressed as a function of the normalized bed height (that is, the ratio of the distance from bed bottom to the expanded bed height). The liquid flow-rate, liquid viscosity and settled bed height influence the mean axial size or density distribution by affecting the expanded bed height.

Chromatography, Liquid↗

[Optimisation of the conditions of particle sizing of gentamicin sulfate].

One of the problems for the development of dry powder inhalation preparations is evaluation of particle size distribution of obtained micronized powders for the determination of theoretical aerodynamic diameter of the particles. The final aim of our study is the development of inhalation dry powder formulation of gentamicin sulfate, therefore it is necessary to determine theoretical aerodynamic diameter of micronized gentamicin sulfate particles. Micronized gentamicin sulfate powders are very cohesive and do not have satisfactory flow properties, the shape of the particles is close to spherical. The most suitable technique for this kind of powders is laser diffraction. On the basis of realized experiments the optimal conditions for the determination of particle size distribution of gentamicin powders were found. Results are in accordance with the data obtained by method-reference (Electron Microscopy).

Administration, Inhalation↗

Ultraviolet disinfection of fecal coliform in municipal wastewater: effects of particle size.

Suspended solids interfere with the efficiency of disinfection using UV radiation by decreasing the rate of disinfection and inducing tailing. However, conventional measures of solids (total suspended solids, turbidity, and UV transmittance) do not adequately predict the presence or degree of these effects. Bacteria and viruses can become associated with particles in wastewater. A fractionation technique was developed to separate particle-associated bacteria into three fractions, based on particle size. The results show that the degree to which particles interfere with UV disinfection efficiency is dependent on particle size. The small size fraction (< 5 microm) consistently produced a statistically significant faster disinfection rate than the large fraction (> 20 microm), with the unfiltered sample and the medium fraction (particles > 5 microm, but < 20 microm) between the two extremes. Tailing also was observed only in the large fraction. Correlations between the disinfection rate constant and the percentage of large fraction bacteria of a sample were good.

Cities↗

Benazepril hydrochloride: effects of particle size on tablet properties.

Tablets manufactured from fine powder (average particle size, D[4,3] = 50.1 microm) benazepril hydrochloride exhibited unacceptable processing and quality properties whereas microcrystalline material (D[4,3] = 4.5-7.7 microm) furnished a product with good processing and quality characteristics.

Algorithms↗