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PubMed2001

[The effect of celiprolol hydrochloride for lipid metabolism--especially for the low density lipoprotein particle size].

Recently, much attention has been paid to small sized low density lipoprotein (LDL) as a risk factor for ischemic heart disease. We investigated the effect of celiprolol hydrochloride (CH), which is a beta 1 selective beta-blocker with high intrinsic sympathomimetic activity (ISA), on the LDL particle size. We treated 41 hypertensive patients with CH and studied the change in LDL particle size according to the score of fast beta lipoprotein and LDL relative mobility value (LDL-Rm) measured by lipoprotein polyacrylamide gel disc electrophoresis (PAGE). We also studied changes in blood pressure, total cholesterol (TC), trygiyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and midband on PAGE. Systolic and dyastolic blood pressure and pulse significantly decreased during treatment. TC levels were significantly decreased at 8 weeks in all subjects and at 4, 8 and 12 weeks in patients with a TC value of over 220 mg/dl. TG levels were significantly decreased at 4 and 8 weeks in patients with initial levels of over 150 mg/dl, and significantly increased at 4 and 8 weeks in those with initial levels of under 150 mg/dl of TG. HDL-C levels did not significantly change during treatment. LDL-C levels were significantly decreased at 4, 8 and 12 weeks in patients with initial levels of over 150 mg/dl. Apo AI, AII, B, CII, CIII and E levels did not significantly change during treatment. Fast beta lipoprotein scores did not significantly change overall during treatment, but were significantly decreased at 4 and 8 weeks in patients initial TG levels of over 150 mg/dl and at 4 and 12 weeks in those with initial levels of over 220 mg/dl of TC. LDL-Rm scores did not significantly change during treatment. Midband scores were significantly reduced overall at 8 weeks, and after 4 and 8 weeks in patients with initial TG levels of over 150 mg/dl and at 4, 8 and 12 weeks in those with initial TC levels of over 220 mg/dl. These results indicated that CH did not change LDL particle size. It was suggested that CH might be a beneficial beta-blocker from the standpoint of prevention for atherosclerosis.

Aged↗

PubMed2006

Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content.

We have produced haloperidol-loaded PLGA/PLA nanoparticles by using two emulsification-solvent evaporation methods: homogenization and sonication. We have established how five independent processing parameters and two materials characteristics control the particle size and drug content. The interdependencies between processing and materials parameters and the subsequent nanoparticle characteristics are discussed in terms of underlying scientific principles that are broadly applicable to the production of drug-loaded polymer nanoparticles. This level of understanding should quicken the pace of designing protocols for making new drug-PLGA nanoparticles. It was determined that the particle size of haloperidol-loaded PLGA/PLA nanoparticles is effectively controlled by the amount of shear stress transferred from the energy source to the organic phase, which is strongly correlated to the following parameters: type of applied energy, aqueous phase volume, and polymer concentration in the organic solvent. The drug content of these nanoparticles is controlled by reducing the diffusion of the drug from the organic to the aqueous phase during the solvent evaporation stage of the preparation and by increasing the drug-polymer interactions. The following significantly inhibit drug diffusion: large particle size, higher polymer concentration and polymer molecular weight, and reducing the drug solubility in the aqueous phase by adjusting the pH. Specific drug-polymer interactions are engineered by optimizing the lactide to glycolide ratio (L:G ratio) and including specific polymer end groups. When optimized, the drug-loaded PLGA/PLA nanoparticles contain as much as 2.5% haloperidol.

Delayed-Action Preparations↗

PubMed1997

Particle size determines the specificity of apolipoprotein E-containing triglyceride-rich emulsions for the LDL receptor versus hepatic remnant receptor in vivo.

Apolipoprotein E (apoE) is an important determinant for the uptake of triglyceride-rich emulsions and lipoproteins by the liver, and exerts affinity for both the LDL receptor (LDLr) and a distinct liver-specific recognition site. Our current aim was to assess the mechanism underlying the receptor-specificity of apoE-carrying lipoproteins. Triglyceride-rich emulsions were synthesized, with mean sizes of 50, 80, and 150 nm. These fractions efficiently acquired apoE from rat serum, and were processed by LPL in vivo with a similar efficiency. Upon injection of the [5H]cholesteryl oleate-labeled emulsions into rats, the liver association rate was positively correlated with particle size (24 +/- 2%, 54 +/- 1%, and 64 +/- 3% of the injected dose at 20 min after injection, respectively) and the liver uptake was predominantly exerted by parenchymal cells. The role of the LDLr in emulsion clearance was established in wild-type versus LDLr knockout mice. In the absence of the LDLr, an 8-fold increased serum half-life was observed for the small emulsion, concomitant with a 6- and 15-fold decreased uptake by the liver and adrenals at 60 min after injection, respectively. In contrast, the in vivo behavior of the large emulsion was independent of the LDLr. Both the ratio of apoE:C on the emulsions upon serum incubation and the alpha-helical content of apoE were inversely correlated with particle size, indicating that these factors may be involved in the emulsion size-dependent receptor specificity in vivo. It is concluded that the contribution of the LDLr to the apoE-mediated clearance of emulsions by the liver and adrenals strongly increases with decreasing particle size, while large particles initially associate with a distinct liver-specific recognition site. As these emulsions mimic chylomicrons, we anticipate that the apoE-dependent metabolic behavior of chylomicrons (remnants) is largely dependent on their size.

Animals↗

PubMed1989

The effect of lactose particle size on the extrusion properties of microcrystalline cellulose-lactose mixtures.

Ram extrusion has been used to assess and compare the flow characteristics and quality of wet powder masses formed from mixtures of water with microcrystalline cellulose and two different particle size samples of lactose. The force-displacement profiles can reveal poor flow properties. Steady state flow was achieved for the mixture containing fine lactose which produced an extrudate of uniform moisture content at all extrusion rates except the lowest (5 cm min-1). Increasing the lactose particle size significantly altered the extrusion properties of the formulation with forced flow predominating and high extrusion pressures observed. Formulations showing that type of extrusion are to be avoided as they produce poor quality extrudate which may be unsuitable for spheronization. Flow visualization studies showed that problems associated with such mixtures are caused by failure to maintain a constant angle of convergence during extrusion, which is essential for maintenance of steady state flow. With the mixture made with coarse lactose, the extrudate quality could be improved by extruding at high velocities, information that may be of significance in the development of formulations for large-scale production. Differences between formulations may be expressed quantitatively by plotting the apparent shear stress-shear rate relationship. The curves are modified by the particle size of lactose included in the mixtures. Such curves have implications in predicting the suitability of an extrudate, produced under particular experimental conditions, for spheronization.

Cellulose↗

PubMed1982

Fractionation of plasma triglyceride-rich lipoproteins of the dairy cow: evidence of chylomicron-size particles.

Electron micrographs of bovine triglyceride-rich lipoproteins demonstrated spherical particles with diameters up to 3000 A. Chylomicron-size particles (larger than 750 A) were isolated specifically by rate zonal centrifugation. Subfractionation by rate zonal centrifugation, isopycnic centrifugation, and gel filtration chromatography all indicated a wide range of bovine triglyceride-rich lipoproteins from chylomicrons to very low density lipoproteins. Chemical analysis of subfractions from gel filtration showed changes in the ratio of triglyceride/protein characteristic of chylomicrons versus very low density lipoproteins. Electrophoretic analysis on agarose gels of bovine chylomicrons obtained by centrifugation and gel filtration showed migrating bands similar to very low density lipoproteins, unlike human chylomicrons. Evidence of bovine chylomicrons provides support for the concept of a significant contribution to milk fat from intestinally absorbed lipid in the dairy cow.

Animals↗

PubMed1985

Particle size distribution of high density lipoproteins as a function of plasma triglyceride concentration in human subjects.

Polyacrylamide gradient gel electrophoresis has been used to examine the particle size distribution of high density lipoproteins (HDL) in human subjects with a wide range of plasma triglyceride concentrations. In studies of groups of both male and female subjects, it was confirmed that the concentration of HDL cholesterol decreases with increasing plasma triglyceride concentration. The HDL fraction from subjects with elevated concentrations of plasma triglyceride was depleted of cholesteryl ester and enriched in triglyceride. It was also confirmed that the proportion of HDL subfraction 2 (HDL2) declines as the plasma triglyceride increases. A new finding was that there were also significant changes in the size of particles in HDL subfraction 3 (HDL3). At low concentrations of plasma triglyceride the predominant subpopulation of HDL3 comprised particles of mean radius 4.3 nm. As the triglyceride concentration increased, however, there was a progressive appearance of HDL3 particles of radius 3.9 nm; in plasma samples with the highest concentrations of triglyceride there was an almost complete disappearance of the 4.3-nm particles, with the population of 3.9-nm particles now predominant.

Adult↗

PubMed1997

Particle size distribution in ground biological samples.

Modern trace and retrospective analysis of Environmental Specimen Bank (ESB) samples require surplus material prepared and characterized as reference materials. Before the biological samples could be analyzed and stored for long periods at cryogenic temperatures, the materials have to be pre-crushed. As a second step, a milling and homogenization procedure has to follow. For this preparation, a grinding device is cooled with liquid nitrogen to a temperature of -190 degrees C. It is a significant condition for homogeneous samples that at least 90% of the particles should be smaller than 200 microns. In the German ESB the particle size distribution of the processed material is determined by means of a laser particle sizer. The decrease of particle sizes of deer liver and bream muscles after different grinding procedures as well as the consequences of ultrasonic treatment of the sample before particle size measurements have been investigated.

Animals↗

PubMed1988

Influence of feed intake, forage physical form, and forage fiber content on particle size of masticated forage, ruminal digesta, and feces of dairy cows.

Two trials were conducted to determine particle size of masticates, ruminal digesta, and feces of dairy cows. In Trial 1, three Holstein cows with ruminal cannulae were fed prebloom alfalfa hay in long, chopped, or pelleted form in a Latin square design (21-d periods) conducted in early lactation (wk 3 to 11) and again during the dry period to attain high (3.75) and low (1.95% of BW) feed consumption. In trial 2, prebloom, midbloom, and full bloom alfalfa hay, mature bromegrass hay, and corn silage were fed to early lactation (wk 5 to 15) Holsteins in a 5 X 5 Latin square design (15-d periods). All diets (Trials 1 and 2) were formulated to 17% CP and contained forage:grain in a 60:40 ratio (DM basis). Similar particle distributions of digesta from long and chopped hay diets suggest little influence of chopping forage on particle size reduction when high quality forage is fed. The large proportion of DM in the small particle (less than .6 mm) pool in the rumen in both trials suggests that rate of escape of small particles from the rumen is an important factor influencing ruminal retention time. Increased proportion of coarse (greater than or equal to 2.36-mm screen) fecal particles at high intake and with fine grinding appears related to a reduction in chewing per unit feed consumed. Soluble DM and particulate matter passing a .063-mm screen made up a significant portion (30 to 50%) of the total DM sieved from all sampling sites in both trials.

Animal Feed↗

PubMed1997

Flow early in the inspiratory manoeuvre affects the aerosol particle size distribution from a Turbuhaler.

Several in vitro and in vivo studies have emphasized the importance of generating a high inspiratory flow when using a dry powder inhaler. Little attention has been paid to the influence of the inspiratory flow profile on the particle size distribution contained in aerosols generated by these devices. The internal volume of a device such as the Turbuhaler is small compared with a vital capacity breath and it is possible that all the powder has been drawn from the device before peak inspiratory flow has been achieved, particularly if the time to peak inspiratory flow is prolonged. A series of experiments were performed to assess the effect of different flow profiles through the Turbuhaler, each with a peak flow of 60 1 min-1. A 400 microgram budesonide Turbuhaler was enclosed in a chamber allowing air to pass unimpeded through the dosing channels and entrainment ports. A large three-way tap was used to blow powder from the device across a Malvern Mastersizer laser particle sizer which produced a profile of the particle size distribution within the aerosol. The rate of increase in flow through the Turbuhaler was determined by the rate at which the three-way tap was turned, and recorded by means of a pneumotachograph. The rate of increase in flow was found to significantly affect the particle size-distribution within the aerosol. Failure to attain a flow of 30 1 min-1 before 150 ml of air had passed through the device resulted in the aerosol volume median diameter increasing from less than 6.6 microns to greater than 45.3 microns. These results indicate that flow during the initial part of the inspiratory effort may be important in determining the characteristics of the aerosol generated by a dry powder inhaler. With more sophisticated equipment, it might be possible to explore the relationship between flow profile and particle size distribution generated by dry powder devices in more detail.

Adult↗

PubMed2006

Influence of particle size distribution on inhalation doses to workers in the Florida phosphate industry.

Previous studies have indicated that inhalation exposures to TENORM aerosols are potentially a major contributor to the annual total effective dose to workers in the Florida phosphate industry. Further research was deemed necessary to characterize the particle size distribution of these aerosols containing various radionuclides of the U decay series. In the present study, individualized assessments of worker committed effective doses are reported in which detailed information is used on the particle size distribution, particle density, particle shape, and radioactivity concentrations from sampled aerosols at 6 different phosphate facilities and at various worker areas within these facilities. Inhalation dose assessments are calculated using the ICRP 66 human respiratory tract model as implemented within the LUDEP and IMBA computer codes. Under the least conservative assumptions of radionuclide-specific lung solubility, the annual total effective doses are shown to be 0.31+/-0.12, 0.27+/-0.07, and 0.22+/-0.02 mSv at granulator, storage, and shipping areas, respectively, and thus all annual doses are below the annual limits to the members of the general public (1 mSv y). In contrast, the most conservative assumptions of lung solubility by radionuclide yield annual total effective doses of 2.24+/-2.53 mSv at granulator areas, 1.26+/-1.19 mSv at storage areas, and 0.56+/-0.36 mSv at shipping areas. In this later case, some 44%, 31%, and 15% of individual dose assessments yield worker doses above the annual dose limit. The study thus demonstrates the importance of facility- and area-specific particle solubility data in dose assessments for regulatory compliance and for making decisions regarding worker respiratory protection.

Aerosols↗

PubMed1989

Effect of particle size of alfalfa hay on intake, digestibility, milk yield, and ruminal cell wall of dairy cattle.

Alfalfa hay was chopped in a tubgrinder containing screens with apertures of 31, 63, or 100 mm. The hays were fed with concentrate to lactating cows (Experiment 1) and without concentrate to nonlactating, fistulated cows (Experiment 2). The objective was to find effects of forage particle size upon intake, digestibility, milk yield, and ruminal cell wall. In Experiment 1, there were no significant effects of forage particle size upon forage or total DM intake, digestibility of NDF, cellulose, nitrogen retained, milk yield, or milk fat percent. Digestibility of DM, ADF, and protein increased as particle size decreased. In Experiment 2, forage DM intake was greater for the 63 than the 100-mm forage but digestibility of cell wall and DM were not different among treatments. Ruminal volume for the 31 and 63-mm forages was greater than the 100-mm forage. Ruminal DM and ruminal cell wall were greater for the 63-mm forage than the 100-mm forage, with the 31-mm forage in between. Increased volume, DM, and cell wall probably account for increased intake of the 63-mm forage. Chopping alfalfa to these three sizes had no particularly positive or negative effects on animal productivity.

Animal Feed↗

PubMed1999

[Effects of alumina particle-size on mechanical properties of alumina-glass composite].

OBJECTIVE: To study the effects of alumina particle-size on mechanical properties of alumina-glass composite. METHODS: Alumina compacts were prepared by isostatic press method and sintered at 1400 degrees C for 2 hours with two various particle-size alumina. Alumina-glass composite was made by infiltrating partially sintered porous alumina with glass at 1200 degrees C for 4 hours. RESULTS: The strength and fracture toughness of nanometre alumina-glass composite were 358.2 MPa, 2.38 MPam1/2 respectively. The strength and fracture toughness of micrometer alumina-glass composite were 432.2 MPa, 5.12 MPam1/2 respectively. Image analysis of SEM micrograph showed that porous rate was about 11.5% in the nanometer alumina-glass composite, 1.2% in the micrometer alumina-glass composite, and there was more glass composition in the nanometer alumina-glass composite than that in the micrometer alumina-glass composite. CONCLUSION: The alumina volume percentage and porous rate play an important role in the strength and fracture toughness of alumina-glass composite.

Aluminum Oxide↗

PubMed1995

Particle size distribution is not the major factor explaining variable analyte transmission efficiency in liquid chromatography/particle beam/mass spectrometry.

We characterized the particle size distribution and the analyte transmission efficiency of a liquid chromatography/particle beam/mass spectrometry (LC/PB/MS) system as a function of experimental variations normally used to optimize the LC/PB/MS system. The particle size distribution was evaluated using an electrical differential mobility particle sizer (DMPS) and both the DMPS and the mass spectrometer were used to evaluate transmission. The latter results were correlated to provide evidence related to mechanisms which contribute to poor sample transmission. Addition of ammonium acetate buffer did not increase the aerosol particle mean diameter. However, it did lead to significant increases in caffeine transmission efficiency observed in both the DMPS and the mass spectrometer. Our results were interpreted to suggest a possible electrostatic cause for quantitative anomalies in LC/PB/MS rather than simple mass discrimination in the particle beam momentum separator.

Aerosols↗

PubMed1974

Urban aerosol toxicity: the influence of particle size.

The basic thesis developed herein is that particle size is an extremely important parameter to consider when assessing the potential toxicity of species present in urban aerosols, and that surface adsorption or condensation greatly promotes toxicity. In the majority of cases this means that particles that are less than 1 micro.m in size are of primary importance. Special significance is attached to the organic constitutents of aerosols. Many of these are known or potential carcinogens and most predominate in extremely small particles which become deposited almost exclusively in the lung.

Adsorption↗

PubMed1994

Improved control over particle sizes and stability of concentrated fluorocarbon emulsions by using mixed fluorocarbon/hydrocarbon molecular dowels.

The use of a surfactant system consisting in equimolar amounts of egg yolk phospholipids and of a mixed fluorocarbon/hydrocarbon amphiphile (C8H17CH = CHC8F17) allows the preparation of concentrated (90% w/v, i.e. 47% v/v) emulsions of perfluorooctyl bromide (perflubron), with average particle sizes ranging from 0.12 to 16 microns post-sterilization, depending on the surfactant/fluorocarbon ratio. Emulsion droplet diameters varied linearly as a function of the emulsifier's concentration, thus allowing easy pre-determination of the emulsion's average particle size. Excellent stability was observed for the dowel-containing emulsions for at least 6 months at 40 degrees C over the whole domain of particle sizes investigated.

Drug Stability↗

PubMed1986

Role of triglyceride-rich lipoproteins and hepatic lipase in determining the particle size and composition of high density lipoproteins.

These studies examined the proposition that the small particle size of HDL3 in the plasma of hypertriglyceridemic subjects is the consequence of the sequential actions of lipid transfer protein and hepatic lipase on HDL. Incubation of unmodified total HDL or HDL3 in the presence of hepatic lipase resulted in a depletion of phospholipid, but little change in the size of the particles. On the other hand, HDL3 that had first been depleted of cholesteryl ester and enriched with triglyceride and phospholipid, during prior incubation with Intralipid and a source of lipid transfer protein, were much more susceptible to the action of hepatic lipase. When these modified HDL3 were incubated with hepatic lipase there was a depletion of the triglyceride and phospholipid content and a conversion into much smaller particles the same size as those predominant in hypertriglyceridemic subjects. These very small particles were derived from a population of modified particles that were larger than the original HDL3 and were within the size range of HDL2. It is proposed, therefore, that in the plasma of hypertriglyceridemic subjects there exists a dynamic balance between the formation of enlarged triglyceride-rich HDL and a secondary conversion of these particles by hepatic lipase to form populations of very small HDL.

Carrier Proteins↗

PubMed2005

Variations of particle size and bed voidage distributions in expanded bed during transient operation processes.

Changes in bed expansion are frequently encountered during an expanded bed adsorption, such as during the initial bed expansion, feed loading and washing processes. We have here studied the changes of local particle size distribution and bed voidage of an expanded bed in the initial bed expansion process as well as those during the changes in mobile phase viscosity, which imitated feed loading and column washing processes. Using a glass column modified with three side sampling ports and Streamline AC as the solid phase, experimental measurements on a series of operation moments during the transient processes were carried out by sampling the particles from within the column at different axial positions. In the initial bed expansion process, the gradual formation of an axial classification from a settled bed to a stable expanded bed was first displayed. By changing the mobile phase from water to 10% (w/w) glycerol solution or vice versa, the variations in both the particle size distribution and bed voidage corresponding to the increase or decrease of the bed height caused by the changes of the mobile phase viscosity were examined as well. The transient changes of the local particle size distribution and bed voidage first occurred in the bed bottom and then progressed from bottom to top along the axial direction. However, the changes of bed voidage at different axial positions were not unidirectional. That is, by changing the mobile phase to the high-viscosity glycerol solution, a constant increase of the bed voidage was observed in the bed bottom, while a distinct decrease of the bed voidage before its increase was involved at the middle and top positions. This is ascribed to the compression effect caused by the upward movement of the lower part particles.

Chromatography↗

PubMed2001

Evaluation of particle size distribution of salmeterol administered via metered-dose inhaler with and without valved holding chambers.

BACKGROUND: Administration of inhaled medications to very young children is sometimes difficult. Administration of inhaled medications via metered dose inhalers (MDIs) to pediatric patients younger than 4 years of age requires use of a holding chamber/spacer with an attached facemask. OBJECTIVE: This in vitro study was conducted to determine the particle size distribution and overall dose of salmeterol delivered in conjunction with the use of various US-marketed valved holding chambers (VHCs) in comparison to the dose-delivered via MDI without VHCs. METHODS: Cascade impaction methodology with high-performance liquid chromatography was used to evaluate the fine particle mass (FPM) of salmeterol administered without and with the use of the following VHCs: Optichamber, medium and large Aerochambers, adult Aerochamber, and medium Aerochamber Plus. RESULTS: Particle size distributions for the Optichamber, various sizes of Aerochamber, and the Aerochamber Plus were very similar and the particle size distributions for all VHCs were similar to the distribution of the control. The FPM for particles ranging from 0.7 to <3.3 microm in diameter (in the range shown to provide the greatest lung dose to negotiate the small airways of infants) was similar across the various VHCs tested. Statistical comparison of the fine particle fraction for these stages shows a very similar profile when differences from the salmeterol MDI control were evaluated. CONCLUSIONS: In vitro results obtained under these test conditions demonstrate that all FPM values for the VHCs tested were within 15% of the control range, a difference that is unlikely to be clinically meaningful. These results indicate that the difference in FPM does not warrant a change in the recommended dosage of salmeterol administered when using the VHCs tested. Our results demonstrate that the use of an MDI and VHC provides a reasonable therapeutic approach for administration of salmeterol MDI to young children and other patients who have difficulties administering the MDI alone.

Administration, Inhalation↗