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Chemical and analytical aspects of areca nut.

A capillary zone electrophoretic (CZE) method for the rapid analysis of the major alkaloids (arecoline and guavacoline) in areca nut extract is described. Areca nuts were pulverized and then extracted with water by sonication in a water bath. After centrifugation, the supernatant was analysed on a fused-silica capillary with 100 mM ammonium acetate-acetic acid (pH 4.6) as the running buffer at a voltage of 20 kV and temperature of 30 degrees C. The method is applicable to the analysis of alkaloids in the nut, commercial preparations (pan masala) and in the saliva of areca nut chewers.

Alkaloids↗

Rapid communication: acute exposure to mercury from dental amalgam does not affect the levels of C-reactive protein or interleukin-6 in peripheral blood.

In a previous study, a significant increase in serum interleukin-6 (IL-6) was apparent after an acute low-level mercury (Hg) exposure, achieved by removal of amalgam fillings (Loftenius et al., 1998). In the present study, 11 healthy volunteers were exposed to an oral dose of 1 g of pulverized amalgam powder. Hg, IL-6, and C-reactive protein (CRP) levels in plasma were followed before and up to 72 h after exposure. The Hg levels were low and stable prior to exposure and increased rapidly after exposure. The median Hg increase was 12.9 nmol/L, which is considerably higher than in the previous study. No significant change over time was observed for IL-6 and CRP levels. Therefore, it cannot be ruled out that our previous finding of increasing IL-6 levels detected after acute low-level Hg exposure through removal of amalgam fillings was due to the dental treatment per se.

Administration, Oral↗

Correlation of nitroaromatic compounds with the mutagenic activity of coal fly ash.

Stack-collected fly-ash particles from a commercial pulverized-coal power plant were extracted with 60/40 w/w benzene-methanol to remove as much of the organic fraction as possible. The extract was sequentially fractionated on a series of high-performance liquid chromatography columns, and the Salmonella bacterial mutagenicity assay using both normal and nitroreductase-deficient strains was used to localize the most mutagenic fractions. Selected fractions were analyzed by a variety of techniques, including gas chromatography with dual-flame ionization and thermionic nitrogen-phosphorus detectors, gas chromatography-mass spectrometry, direct-probe low-resolution or low-voltage mass spectrometry, and high-resolution mass spectrometry. Mutagenicity data indicated that nitroorganic compounds were the primary mutagens in all samples submitted for chemical analysis. A series of homologous alkylated nitrophenanthrenes appear to be important mutagens in one major fraction, while alkylated nitrofluorenones appear to be the dominant mutagens in a second major fraction. No nitro compounds were identified in a third major fraction. In addition to the nitro compounds, substantial amounts of fluorenones were also found, although these are not believed to contribute to the direct-acting mutagenic activity of the samples.

Animals↗

Isolation and characterization of fly ash from rat lung tissue.

Inhaled fly ash may be leached by lung fluids, making potentially toxic trace elements in the fly ash bioavailable. We studied the composition and morphology of fly ash particles recovered from lungs of rats exposed to fly ash from a power plant burning pulverized eastern coal. Animals were sacrificed 1, 3, 6, and 12 mo after the commencement of the 4-wk exposures. Particles isolated from lungs of exposed animals, control fly ash samples, and samples recovered from control lungs spiked with fly ash were characterized by computer-controlled scanning electron microscopy (CCSEM) and thin window energy dispersive X-ray spectroscopy (EDS). EDS spectra of fly ash and ashed lung residues were distinct. Thus, fly ash particles could be distinguished from ashed lung residues. A majority of the fly ash particles recovered from lungs of exposed animals had similar morphology and composition to the exposure material. However, the number of silicon-rich particles decreased with time. After 6 mo, about 1% by number of the particles had been transformed, producing numerous "needles" associated with residues of fly ash particles. Particles that looked like diatoms were observed. This demonstrated that the sample preparation procedures used did not destroy delicate structures. Fly ash particles from a spiked control lung subjected to the same separation procedures did not have these structures. The structures may be the result of leaching of particles by lung fluids, which suggests that the glassy matrix components of fly ash particles may be bioavailable.

Animals↗

Grain dusts and grain plant components vary in their ability to recruit neutrophils.

Occupational exposure to grain dusts can cause bronchitis, particularly to grain sorghum dust. Bronchitis is associated with the presence of increased numbers of neutrophils. To determine how grain dusts could cause neutrophil recruitment to the airways, extract of whole-grain sorghum, corn, and soybean dusts and of pulverized components of these plants were made with Hanks balanced salt solution (HBSS) and used in direct neutrophil chemotaxis experiments. The glume of the grain sorghum plant, the structure holding the seeds in place, caused the migration of the greatest number of neutrophils compared to HBSS [132 +/- 7 vs. 60 cells/high-power field (hpf) +/- 2 SEM, p < .001], followed by whole-grain sorghum dust (121 +/- 5 cells/hpf). Next, bovine bronchial epithelial cells (BBECs) were obtained from fresh lungs and grown to near confluence before challenge with a 10% solution of grain dust and grain plant extracts. The grain sorghum glume and whole-grain sorghum dusts caused release of the greatest amount of neutrophil chemotactic activity (NCA) from BBECs compared to the medium M199 negative control (141 +/- 6 and 153 +/- 7, respectively, vs. 64 cells/hpf +/- 3 SEM, p < .001). The ability to cause neutrophils to migrate by direct and indirect means did not correlate with levels in the grain dusts of endotoxin, which is known to cause release of NCA from bronchial epithelial cells. Therefore, this article describes additional mechanisms by which grain dusts can cause pulmonary inflammation and that are independent of endotoxin levels.

Animals↗

Aerosol generation to simulate specific industrial fine particle effluents.

Techniques were developed for generating large quantities of fine particle metal oxide aerosols. The aerosols were generated by burning flammable solutions containing appropriate soluble compounds (nitrates, for example) of the desired elements. In the flame these compounds generally decomposed to oxides. The generated aerosol flow rates were as high as 42 m3 per minute (1500 cfm); the mass concentrations were as high as 16.8 g per m3 at STP. For most aerosols the particle concentrations were of the order of 10(9) particles per cm3. Electron microscopic pictures (SEM and TEM) of precipitated particles show that many of the larger particles (20 microm) are hollow and that the smaller particles (0.01 microm) are aggregated. Specific aerosols were generated to simulate the fine particulate effluents generated by combustion of pulverized coal (electricity generation) electric arc and basic oxygen furnaces (iron and steel production) and zinc smelters. Methods were developed to vary the sulfur dioxide concentration and the electrical resistivities of the simulants for coal combustion.

Aerosols↗

Assessing truck driver exposure at the World Trade Center disaster site: personal and area monitoring for particulate matter and volatile organic compounds during October 2001 and April 2002.

The destruction of the World Trade Center (WTC) in New York City on September 11, 2001, created a 16-acre debris field composed of pulverized and burning material significantly impacting air quality. Site cleanup began almost immediately. Cleanup workers were potentially exposed to airborne contaminants, including particulate matter, volatile organic compounds, and asbestos, at elevated concentrations. This article presents the results of the exposure assessment of one important group of WTC workers, truck drivers, as well as area monitoring that was conducted directly on site during October 2001 and April 2002. In cooperation with a local labor union, 54 drivers (October) and 15 drivers (April) were recruited on site to wear two monitors during their 12-hour work shifts. In addition, drivers were administered a questionnaire asking for information ranging from "first day at the site" to respirator use. Area monitoring was conducted at four perimeter locations during October and three perimeter locations during April. During both months, monitoring was also conducted at one location in the middle of the rubble. Contaminants monitored for included total dust (TD), PM10, PM2.5, and volatile organic compounds. Particle samples were analyzed for mass, as well as elemental and organic carbon content. During October, the median personal exposure to TD was 346 microg/m3. The maximum area concentration, 1742 microg/m3, was found in middle of the debris. The maximum TD concentration found at the perimeter was 392 microg/m3 implying a strong concentration gradient from the middle of debris outward. PM2.5/PM10 ratios ranged from 23% to 100% suggesting significant fire activity during some of the sampled shifts. During April, the median personal exposure to TD was 144 microg/m3, and the highest area concentration, 195 microg/m3, was found at the perimeter. During both months, volatile organic compounds concentrations were low.

Air Pollutants↗

[Dynamics of amino acid and protein metabolism in laying hens after the administration of 15N-labeled wheat protein. 11. Incorporation of 15N in the tissues and the amino acids of the muscles].

Over a period of 4 days 12 colostomized laying hens daily received 36 g 15N labelled wheat with 15N excess (15N') of 14.37 atom-% together with a conventional feed mixture for laying hens. The labelling of the lysine N in the wheat was 13.58 atom-%, that of histidine N 14.38 and that of arginine 15N' 13.63 atom-% 15N'. Three hens each were butchered 12, 36, 60 and 108 h after the last 15N' feeding. The first three hens did not receive any feed before being butchered. The following three hens each received the unlabelled feed ration for another 1, 2 or 4 days resp. after the main period until they were butchered. The total of skeleton muscles, the heart and the stomach muscle (without inner skin) of each hen were combined into one sample, cut thinly, drenched with fluid nitrogen and pulverized. N, 15N' and the basic and non-basic amino acids as well as their 15N' were determined in the individual samples. In contrast to the organs, the proteins in the muscle tissue have a long half life so that a slight decrease of atom-% 15N' in the muscles could only be detected after 108 h. The 14N and 15N' quota of the non-basic amino acids in the total nitrogen of the muscles is 50%. The 14N quota of the basic amino acids is 30% and the 15N' quota only 22.5% in the total muscle N. The heavy nitrogen of the free lysine in the TCA soluble N fraction is hardly detectable 36 h and 60 h after the last 15N' supply and not at all after 108 h. In contrast to this, the other two free basic amino acids remain significantly higher labelled in dependence on the last butchering time.

Amino Acids↗

Study of load capacity of Avicel PH-200 and Cellactose, two direct compression excipients, using experimental design.

The load capacity of two excipients, a large particle size grade of microcrystalline cellulose (Avicel PH-200) and a coprocessed material composed of lactose and pulverized cellulose (Cellactose) was determined using a model mix with Dipyrone (metamizol sodium) and experiments planned by design of experiments. A multiple-regression model was proposed, and as a result, a new parameter, called specific load capacity SLC was obtained. This constant can be determined for other excipients and drugs; it depends only on the excipient and the drug used.

Anti-Inflammatory Agents, Non-Steroidal↗

Modification of crystal habit of ibuprofen using the phase partition technique: effect of aerosil and tween 80 in binding solvent.

A ternary diagram, representing the solubility of binding solvent (chloroform) in a mixture of ethanol and water, was constructed. For this study, the solvent mixture that gave the best ibuprofen pellets (IPs) was composed of chloroform.ethanol:water at a ratio of 1.5%:8%:90.5%. The suitable agitator speed, temperature, and mixing time were found to be 1,500 rpm, 25 degrees C +/- 2 degrees C, and 20 min, respectively. In addition, suitable stirring time when the phase partition process of IPs began was 15 min. IPs obtained from these conditions were small and round, approximately 1 mm; surface determination by scanning electron microscopy (SEM) indicated that the IPs were composed of drug microcrystals rearranged on the surface. For the dissolution, IPs showed lower drug release when compared with pure ibuprofen crystal (IC) (f2 analysis). An attempt to modify the dissolution property of IP by incorporating various concentrations of Aerosil and Tween 80 in the binding solvent was made. Microscopic appearance showed that both Aerosil and Tween 80 gave less spherical pellets when compared with the use of binding solvent alone. For both the Aerosil and Tween 80 employed, the results indicated a change in rearrangement of drug microcrystals and a change in crystal habit. However, Tween 80 gave more change of the crystallographic direction of drug microcrystals than Aerosil. In term of dissolution, the results showed that employing Tween 80 at 1.2% gave the highest drug release compared to the use of Aerosil and IC alone (f2 analysis). These pellets had a good flow property, as indicated by Carr's compressibility, flow rate, and angle of repose, and they can be compressed into a tablet, encapsulated by suitable polymer, or pulverized to obtain micronized crystals. In the case of compression into tablets, the dissolution profiles of these tablets compared with those of commercial product meet the USP 24 requirement (Q > or = 80% at 60 min).

Crystallization↗

Preparation and characterization of glassy celecoxib.

Celecoxib, a poorly water-soluble drug, was converted into a glassy state by melt quenching. The properties of glassy celecoxib were studied using infrared (IR) spectroscopy, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), intrinsic dissolution rate (IDR), and thin-layer-chromatography (TLC). Glass transition occurred at 51.8 degrees C. Infrared spectrum of glass has revealed significant changes due to H-bonding. Celecoxib glass shows around 15 times faster dissolution as compared with the crystalline state. Heckel plot analysis has shown better compressibility in glassy state. Unpulverized glass remained stable for 3 months, whereas after pulverization about 70% crystallinity was gained in 100 hours. Further attempts may be carried out to stabilize the glass.

Calorimetry, Differential Scanning↗

A study of the components of the cornified epithelium of human skin.

Pulverized cornified epithelium of human skin was divided into a "soluble fraction" and a "residue." About half of the "soluble fraction" proved to be soluble epidermal keratin (keratin A); the remainder, dialyzable substances of low molecular weight. The "residue" contained epidermal keratin and resistant cell membranes of cornified cells. Epidermal keratin was found to form an oriented and dense submicroscopic structure in the cornified cells. It showed high resistance toward strong acid and moderately strong alkali solutions as well as concentrated urea. In strong alkali, reducing substances, alkaline urea, and mixtures of reducing substance with alkali, epidermal keratin dissociated and yielded a non-dialyzable derivative of high molecular weight (keratin B) which resembled true proteins. The cell membranes of cornified cells showed higher resistance toward strong alkali and reducing substance than did epidermal keratin.

Cell Membrane↗

Induction of prophase in interphase nuclei by fusion with metaphase cells.

Fusion of an interphase cell with a metaphase cell results in profound changes in the interphase chromatin that have been called "chromosome pulverization" or "premature chromosome condensation" In addition to the usual light microscopy, the nature of the changes has been investigated in the present study with electron microscopy and biochemical techniques Metaphase and interphase cells were mixed and fused at 37 degrees C by means of ultraviolet-inactivated Sendai virus. After cell fusion, morphological changes in interphase nuclei occurred only in binucleate cells which contained one intact set of metaphase chromosomes Irrespective of the nuclear stage at the time of cell fusion, the morphologic changes that occurred 5-20 min later simulated very closely a sequence of events that characterizes the normal G(2)-prophase transition. Radioautography revealed that, late in the process, substantial amounts of RNA and probably protein were transferred from the interphase nucleus into the cytoplasm of fused cells. Thus, the findings indicate the existence in metaphase cells of factor(s) which are capable of initiating biochemical and morphological events in interphase nuclei intrinsic to the normal mitotic process.

Animals↗

Bacteriological validation of a new apparatus for disinfection of hospital waste at the point of disposal.

OBJECTIVES: To evaluate the ability of a new apparatus (Dipsys 25, Société SGN, Bagnols sur Cèze, France) to disinfect biomedical waste, including both potentially infectious agents and the normal saprophytic flora of the waste. METHODS: Disinfection was assessed using standard methods (reference strains were fixed on reference carriers according to the French AFNOR methods) and nonstandard assays. Assays in conditions of hospital use, evaluations of bacterial survival during storage, sporicidal effect, and spore survival during storage were performed in parallel. Finally, bactericidal effect in extreme conditions (association of high contamination and high bacterial protection conditions) was tested with normal fecal flora. Bacterial counts were performed after treatment by the apparatus and without treatment (controls). All tests were carried out in triplicate. RESULTS: In all treated carriers, a bacterial population decrease of at least 5 log10 was obtained. Assays performed in hospital-use conditions did not show any bacterial growth. Concerning the evaluation of sporicidal effect and spore revival during conservation, a minimum reduction of 5 log10 was observed in all assays performed, without survival. Finally, concerning assays in extreme conditions, the decrease of bacterial population was between 5 log10 and 10 log10 for vegetative anaerobes of normal fecal flora. CONCLUSION: Under our study conditions, the study apparatus reduced the tested microbial populations by a minimal factor of 5 log10. The main advantage of the apparatus is the opportunity to treat contaminated waste inside hospital wards, at the point of initial collection, without pulverization, by nonspecialized staff.

Bacteria, Aerobic↗

Tablet formulation of levothyroxine is absorbed less well than powdered levothyroxine.

The comparative bioavailability of oral doses of levothyroxine (LT(4)) formulation taken as tablets, after being crushed, or chewed before swallowing has not been well studied. Three patients with hypothyroidism who showed persistent elevation of serum thyrotropin (TSH) despite taking 200, 150, and 125 microg of LT(4) tablets per day are presented. They did not show signs and symptoms of gastrointestinal illness that could interfere with the absorption of LT(4) nor history of such a condition. They did not concurrently take medications known to affect the absorption of LT(4) from the gut. Their serum TSH levels normalized when the tablets were taken after being pulverized. The difference appeared attributable to the slow dissolution of the tablets in the gut of these patients.

Adult↗

Reducing shock number dramatically decreases lesion size in a juvenile kidney model.

BACKGROUND AND PURPOSE: Adult stone patients are treated with several thousand lithotripter shockwaves (SWs) in order to pulverize a kidney stone. This typical clinical dose assures that the stone will be fractured completely. However, this same dose induces damage to the kidney, especially pediatric-size kidneys. If increasing SW number is known to increase renal injury and functional impairment, will reducing SW number below typical treatment levels significantly decrease kidney damage and hemodynamic changes? MATERIALS AND METHODS: To address this question, one kidney in each of nine juvenile pigs (6-7 weeks old) was treated with 1000 SWs at 24 kV directed at a lower-pole calix with an unmodified HM-3 lithotripter. Parenchymal-lesion size was determined by sectioning the entire kidney and quantitating the amount of hemorrhage in each slice. Renal function was determined before and after SW treatment by inulin clearance, paraaminohippurate (PAH) extraction, and PAH clearance. The resulting morphologic and functional changes were then compared with those of kidneys that had been treated with a typical clinical dose of 2000 SWs (data previously published; J Am Soc Nephrol 2000;11:310). Eleven pigs were utilized as sham-treated controls. RESULTS: Limiting SW number to 1000 significantly reduced the size of the lesion (by 95%) and reduced the degree of functional change (glomerular filtration rate by 38%, PAH extraction by 73%, renal plasma flow by 46%) compared with kidneys receiving 2000 SWs (an adult dose). CONCLUSIONS: These data support the idea that SW number should be reduced to the lowest number that fractures kidney stones in order to minimize renal injury and functional impairment.

Animals↗

Physical characteristics and health effects of aerosols from collapsed buildings.

Airborne pollutants can rise to extreme levels when large buildings fall down. The terrorist attack on New York's World Trade Center (WTC) towers caused the release of an enormous quantity of pulverized building materials and combustion products into the local environment. Particulate matter (PM) from crushed WTC building materials is primarily non-respirable (>96% larger than 10 microm mass median aerodynamic diameter [MMAD]) and composed of fibrous and nonfibrous components such as gypsum, calcite, silica, glass fibers, cellulose, and asbestos. Respirable fine WTC PM (PM(2.5)) may include finely crushed building materials as well as combustion products such as dioxins and polycyclic aromatic hydrocarbons (PAHs). Rescue workers at the WTC site had exposure-related increases in the incidences of nasal congestion, bronchial hyperreactivity to aerosolized methacholine, gastroesophageal reflux disease, and persistent cough. Toxicological studies in mice indicate that WTC PM(2.5) causes airflow obstruction above a critical dose. The review of physical characteristics and health effects of major pollutants derived from the collapse of the WTC towers has assisted in risk assessment efforts related to the collapse of large buildings.

Aerosols↗

Alert to users of calcium supplements as antihypertensive agents due to trace metal contaminants.

Although there are controversies in the role of calcium as an antihypertensive agent, the use of "health food" supplements, such as dolomite and bone meal, is on the rise especially among the older population. One brand of commercial dolomite tablets were investigated for metallic contents such as aluminum (Al), arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), sclemium (Se), and zinc (Zn). Ten randomly selected tablets were weighted, dried, pulverized and low-temperature plasma ashed. An ash aliquot of each tablet was dissolved in 35% Ultrex nitric acid, and after dilution analyzed using a Perkin-Elmer Model 5000 atomic absorption spectrophotometer equipped with an HGA-500 graphite furnace, As-1 autosampler, and PRS-10 printer sequencer. The results (presented as mean wt/g of powder +/- 95% confidence limits) are: Al 900 +/- 300 micrograms/g; As 1.3 +/- 0.3 micrograms/g; Cd 0.16 +/- 0.04 micrograms/g; Cr 5.9 +/- 1.4 micrograms/g; Cu 3.0 +/- 0.6 micrograms/g; Pb 1.9 +/- 0.5 micrograms/g; Mn 66 +/- 7.0 micrograms/g; Se 1.6 +/- 0.4 micrograms/g; and Zn 147 +/- 88 micrograms/g. These trace metals could pose health hazards to the public such as lead poisoning, dementia, and hypertension due to cadmium. Also, zinc can potentiate cadmium-hypertensive effects. The need exists to initiate some regulations to limit maximal content of trace metals in "health food" supplements to protect high-risk groups and that sector of the population who use megadoses of such products.

Antihypertensive Agents↗