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Method development and validation for zotarolimus concentration determination in stented swine arteries by liquid chromatography/tandem mass spectrometry detection.

Drug-eluting stents have attracted significant attention in the medical community and pharmaceutical industry due to their proven success in significantly reducing restenosis. Abbott Laboratories is developing a drug-eluting stent coated with zotarolimus and swine was recently used as an animal model for the pre-clinical study of stent implantation. In this article, we present a detailed experimental design and results for the validation and sample analysis of zotarolimus drug concentration in stented swine artery samples. Introduction of tissue quality control (QC) samples allows evaluation of the entire analytical process as well as the stability of the drug in both original tissue and homogenized tissue samples. In addition, a novel approach using 100% swine blood as the homogenization solution was developed for the consistency of the liquid-liquid extraction recovery and stability of the zotarolimus in tissue homogenates. Standards were prepared by spiking zotarolimus working solution in swine blood and tissue QC samples were used along with the artery samples during the sample analysis. The linear dynamic range of blood standard samples is from 0.61 to 333.20 ng/mL to accommodate the predicted artery homogenate concentrations. Overall tissue QC %CV during the method validation was from 4.4% to 8.6%. The overall %bias of tissue QC samples during the method validation was from -7.3% to 16.6%. The method was successfully applied for the analysis of swine artery samples. A similar approach for method validation and sample analysis has been successfully applied for the analysis of swine myocardium, kidney and liver tissue samples.

Animals↗

Anthropogenically derived mercury in sediments of Pialassa Baiona, Ravenna, Italy.

Pialassa Baiona, a coastal wetland near the city of Ravenna, has been impacted for two decades (1958-1978) by industrial discharges containing mercury and floating agglomerates of residues of polymerization processes. Although the industrial use of mercury completely ceased in the early 90's, surface sediments are still highly contaminated, mercury concentrations decreasing from the southern sub-basin, close to the discharge point, to the farthest northern border. Concentrations of total mercury, synthetic polymers (determined by pyrolysis-GC/MS), total organic carbon, C/N ratio, total sulfur and 210Pb dating, were determined in sediment cores collected in the southern and northern sub-basins. Mercury and polymers exhibited parallel profiles with a peak corresponding to the historic emission record in the southern core, while in northern cores peaks of maximum concentration display a delay reflecting the time required for the pollutants to migrate. A recently developed mercury sequential extraction procedure was applied to the most polluted layers to study inorganic mercury speciation. Results indicate differences between the southern and northern areas, suggesting a more efficient binding of mercury to sediments in the southern sub-basin.

Environmental Monitoring↗

Removal of selenocyanate from water using elemental iron.

Batch experiments were conducted to investigate the removal of selenocyanate (SeCN-) from oil refinery wastewater and artificial wastewater with elemental iron [Fe(0)]. The chemical forms of selenium in the reacted solids were determined with X-ray photoelectron spectroscopy (XPS) and a sulfite extraction procedure. SeCN- was effectively removed from the wastewater with Fe(0) filings when the water pH was controlled at approximately 6. SeCN- was removed by Fe(0) through the formation of elemental selenium [Se(0)] and ferrous selenide. The possible chemical reactions between SeCN- and Fe(0) included deselenation of SeCN- and electrochemical reduction of Se(0) to selenide. A cost-effective process may be developed for the treatment of SeCN- in wastewater using Fe(0).

Cyanates↗

Development of a profitable procedure for the extraction of 2-H-1-benzopyran-2-one (coumarin) from Mikania glomerata.

This report deals with a new procedure suitable for the extraction of coumarin 1 from Mikania glomerata. The aim of this investigation is to obtain this compound in an economically profitable way, taking into account the yield of its extraction, the cost, and the time of the overall process. Fresh and dried plants collected in several areas of the State of Rio de Janeiro were used, and seasonal effects on coumarin content were studied. Obtained results indicated that extraction with a 1% (w/v) NaOH solution, under appropriate conditions, allows a simple and complete recovery of the desired product and that the best yields were obtained with the fresh aerial parts of the plant. Season and area of harvesting effects have also been studied.

Costs and Cost Analysis↗

Time- and concentration-dependent effects of dissolution products of 58S sol-gel bioactive glass on proliferation and differentiation of murine and human osteoblasts.

Bone loss is a significant clinical problem, and treatments utilizing donated graft material are limited. To meet future demands in the healthcare industry, there has been a shift of outlook toward the use of bioactive materials for tissue regeneration. A number of in vivo and in vitro studies have highlighted the potential of the bioactive glass ceramic 45S5 Bioglass as a synthetic regenerative scaffold. The application of sol-gel processing techniques has led to the synthesis of mesoporous bioactive glasses with greater textural and compositional variety. In this study, we evaluated the effects of supplemented tissue culture medium containing up to 203 ppm silica prepared by static soaking of particles of 58S sol-gel bioactive glass (58% SiO(2), 33% CaO, 9% P(2)O(5)) on the in vitro proliferation and differentiation of murine and human primary osteoblasts. These extracts had a higher silica content than those used previously in studies of 45S5 Bioglass, because of the faster rates of ion exchange permitted by the higher surface area-to-volume ratio of mesoporous glass. We found that osteoblasts from both species increased their proliferation in response to the glass-conditioned medium. In addition, the extent to which supplemented medium could alter cell differentiation varied with time in culture. Proliferation induced by supplemented medium paralleled effects induced by treatment with basic fibroblast growth factor, a known mitogenic growth factor for osteoblasts. Bone nodule formation was also increased by exposure to the glass-conditioned medium and this effect was positively correlated with the dose of glass used to prepare the medium. Apoptosis was stimulated by glass-conditioned medium in murine osteoblasts, but inhibited in human osteoblasts. These data demonstrate the bioactive effects of dissolution products derived from sol-gel materials on primary osteoblasts and complements in vivo studies that indicate the suitability of this material as a bone graft substitute.

Animals↗

Occupational asthma from inhaled egg protein.

We evaluated workers and performed an industrial hygiene assessment at a plant where raw eggs are processed into powdered egg yolk and whole egg. Egg dust levels in the packaging room straddled the American Conference of Governmental Industrial Hygienists' (ACGIH) exposure guideline of 10 mg/m3 for nuisance dust. We obtained medical histories from 25 workers, and performed physical examinations, spirometry, and serial determinations of peak expiratory flow rate (PEFR) by portable meter every 3 hrs (while awake) for 7 days. We defined symptomatic bronchial lability to be a decrement in PEFR on any one day of 20% or more of the day's maximum, with concurrent symptoms. Skin-prick tests and serum assays for specific IgE by the radioallergosorbent (RAST) method were performed to assess sensitivity to commercial egg proteins, egg protein fractions, and freshly prepared extracts of whole egg powder and yolk. We classified participants as definite cases of asthma if both the examining physician diagnosed asthma and symptomatic bronchial lability was demonstrated by serial PEFR determinations. Definite noncases of asthma were those participants in whom the physician did not diagnose asthma and in whom symptomatic bronchial lability was not demonstrated by PEFR. All five definite cases, compared to three of 16 definite noncases of asthma, had one or more positive skin-prick tests to egg proteins. Four of five cases, compared to 0 of 14 noncases, who had serum determinations, had an elevated RAST to one or more of the egg proteins. This study demonstrates that occupational asthma associated with IgE-mediated allergy to egg proteins occurs among workers exposed to inhaled egg proteins.

Air Pollutants, Occupational↗

[Cluster cases of malignant pleural mesothelioma in an oil factory].

BACKGROUND: The traditional occupational hazards of the productive cycle of oils are attributable to chemicals (use of solvents, pesticides and other agents), dusts, labour accidents (trauma, ignition, explosion), noise, manual lifting, work organization and hot-wet microclimate. The latest risk is due to the use of high temperatures (from 50 up to 250 degrees C) during the processes of extraction with solvent and refining. No cases are reported in literature of asbestos related disease in subjects who worked in oil factories. Nevertheless the structure and organization of the workplace, which is similar to that of sugar refineries, where cases of malignant mesothelioma have been described (moreover in workers employed in running and maintenance of the plants), led to the assumption that even in oil factories asbestos for the insulation of pipes and boilers could be present. OBJECTIVES: To describe 3 cases of Malignant Mesothelioma that occurred in workers of the same oil factory. METHODS: Since this occupational sector is not conventionally known for asbestos exposure the Local Health Unit and the Lombardy Mesothelioma Registry decided to investigate this industrial plant. RESULTS: Following examination of the archives of the Local Health Unit and inspection of the plant, an environmental asbestos contamination (pipes and boilers) was found. The 3 cases were defined as occupational disease and the required legal procedures were initiated. This underlines the importance of close cooperation with Local Health Units of occupational medicine and the Regional Mesothelioma Registry in the study and acknowledgment of cases which would otherwise not have been recognized, with consequent loss of precious information.

Aged↗

Prevalence of occupational asthma in silk filatures.

A clinical survey in two silk filatures revealed that 36.2% of the persons engaged in the processing of natural silk were suffering from bronchial asthma, while 16.9% of the total subjects had asthma of occupational origin. Skin prick tests using crude silkworm cocoon and pupal allergen extracts revealed that 28.8% of the subjects were sensitive to the silkworm-derived allergens. IgE antibodies specific to both cocoon and pupal allergens were demonstrable by RAST in the sera of patients with positive skin reactions and occupational asthma.

Antibody Specificity↗

Extraction of equine chorionic gonadotrophin from pregnant mare plasma by direct adsorption on chromatographic media.

Equine chorionic gonadotrophin (eCG) is a hormone of practical value in veterinary medicine and animal production. Here we report a novel preparation procedure based on its direct adsorption onto anionic-exchange resins in a batch-wise mode. The active plasma is previously conditioned to reduce pH and ionic strength to required levels. After the adsorption stage, a 90% recovery of the initial eCG is achieved, with a concentration factor of about 50 and an enrichment factor around 500, with high preservation of biological activity. Further purification is carried out by cation-exchange column chromatography. The recovery for the whole process is higher than 70%, and the final potency of the preparation is close to 4000 IU/mg. The process is well suited for its application to the industrial scale.

Adsorption↗

Purification of lipases.

Interest on lipases from different sources (microorganisms, animals and plants) has markedly increased in the last decade due to the potential applications of lipases in industry and in medicine. Microbial and mammalian lipases have been purified to homogeneity, allowing the successful determination of their primary aminoacid sequence and, more recently, of the three-dimensional structure. The X-ray studies of pure lipases will enable the establishment of the structure-function relationships and contribute for a better understanding of the kinetic mechanisms of lipase action on hydrolysis, synthesis and group exchange of esters. This article reviews the separation and purification techniques that were used in the recovery of microbial, mammalian and plant lipases. Several purification procedures are analysed taking into account the sequence of the methods and the number of times each method is used. Novel purification methods based on liquid-liquid extraction, membrane processes and immunopurification are also reviewed.

Animals↗

Effects of composting process and fly ash amendment on phytotoxicity of sewage sludge.

With the increasingly growing global production of sewage sludge, evaluation of its applicability in agriculture and land restoration is essential. This study assessed the potential effects of composting process and fly ash amendment on soil-ameliorating properties of sewage sludge. The metal availability and phytotoxicity of ash-amended sludge compost (AS, mature sewage sludge compost mixed with fresh lagoon ash) and sludge-ash co-compost (SA, co-composted mixture of sewage sludge and lagoon ash) were compared. The results of this work suggested that both composts favored the applicability of sewage sludge for land application by reducing Cd, Cu, Pb, and Zn availability. The SA co-compost stimulated seed germination at ash amendment rates of < or = 10%, whereas various treatments of AS compost inhibited germination at an extract dilution of 50%. Amendment of lagoon ash before or after sludge composting increased electrical conductivity (EC) and volatilization of NH4-N, but lowered availability of PO4-P. Together with the results of phytotoxicity, an optimal ash amendment rate of 5% for AS and 10% for SA were most desirable. Alkaline amendment prior to sludge composting was recommended, because it could be more effective in reducing soluble and plant-available metal concentrations through the composting process.

Carbon↗

Optimization of an ethanol production medium in very high gravity fermentation.

Concentrations of Mg(2+), glycine, yeast extract, biotin, acetaldehyde and peptone were optimized by a uniform design process for ethanol production by Saccharomyces cerevisiae. Using non-linear step-wise regression analysis, a predictive mathematical model was established. Concentrations of Mg(2+) and peptone were identified as the critical factors: 50 mM Mg(2+) and 1.5% (w/v) peptone in the medium increased the final ethanol titre from 14.2% (v/v) to 17% (v/v) in 48 h.

Acetaldehyde↗

Characterization of the volatile fraction emitted by phloems of four pinus species by solid-phase microextraction and gas chromatography-mass spectrometry.

Pine forests constitute some of the most important renewable resources supplying timber, paper and chemical industries, among other functions. Characterization of the volatiles emitted by different Pinus species has proven to be an important tool to decode the process of host tree selection by herbivore insects, some of which cause serious economic damage to pines. Variations in the relative composition of the bouquet of semiochemicals are responsible for the outcome of different biological processes, such as mate finding, egg-laying site recognition and host selection. The volatiles present in phloem samples of four pine species, P. halepensis, P. sylvestris, P. pinaster and P. pinea, were identified and characterized with the aim of finding possible host-plant attractants for native pests, such as the bark beetle Tomicus piniperda. The volatile compounds emitted by phloem samples of pines were extracted by headspace solid-phase micro extraction, using a 2cm 50/30mm divinylbenzene/carboxen/polydimethylsiloxane table flex solid-phase microextraction fiber and its contents analyzed by high-resolution gas chromatography, using flame ionization and a non polar and chiral column phases. The components of the volatile fraction emitted by the phloem samples were identified by mass spectrometry using time-of-flight and quadrupole mass analyzers. The estimated relative composition was used to perform a discriminant analysis among pine species, by means of cluster and principal component analysis. It can be concluded that it is possible to discriminate pine species based on the monoterpenes emissions of phloem samples.

Animals↗

From genomics to chemical genomics: new developments in KEGG.

The increasing amount of genomic and molecular information is the basis for understanding higher-order biological systems, such as the cell and the organism, and their interactions with the environment, as well as for medical, industrial and other practical applications. The KEGG resource (http://www.genome.jp/kegg/) provides a reference knowledge base for linking genomes to biological systems, categorized as building blocks in the genomic space (KEGG GENES) and the chemical space (KEGG LIGAND), and wiring diagrams of interaction networks and reaction networks (KEGG PATHWAY). A fourth component, KEGG BRITE, has been formally added to the KEGG suite of databases. This reflects our attempt to computerize functional interpretations as part of the pathway reconstruction process based on the hierarchically structured knowledge about the genomic, chemical and network spaces. In accordance with the new chemical genomics initiatives, the scope of KEGG LIGAND has been significantly expanded to cover both endogenous and exogenous molecules. Specifically, RPAIR contains curated chemical structure transformation patterns extracted from known enzymatic reactions, which would enable analysis of genome-environment interactions, such as the prediction of new reactions and new enzyme genes that would degrade new environmental compounds. Additionally, drug information is now stored separately and linked to new KEGG DRUG structure maps.

Biotransformation↗

Tuning the diffusion dialysis performance by surface cross-linking of PPO anion exchange membranes--simultaneous recovery of sulfuric acid and nickel from electrolysis spent liquor of relatively low acid concentration.

The results of the development of the industrial diffusion dialysis technology and the unit based on it for sulfate acid recovery from nickel electrolysis waste have been considered. Unlike most acid recovery systems, this system has a relatively low acid concentration and the main aim is to recover both nickel and acid sulfate by recycling the waste and the recovered acid to the respective steps of electrolysis process. So the waste volume control seems to be the most important thing. To satisfy with this new request, the membrane is surface-cross-linked with aqueous ammonium to decrease waste volume expansion caused by the water osmosis. The results showed that the best membrane for such operation is the one that cross-linked at least 8 h with a volumetric expansion factor (volumetric ratio of waste to feed) less than 1.1. Pilot diffusional runs were conducted with this membrane at various feed flow rate and flow ratio of stripping water and feed. After comprehensively considering all factors, the range of feed flow and the flow ratio has been recommended to be 1.2-1.8 l/h and 1.05-1.1, respectively. Under these conditions, nickel leakage can be controlled within 4% and the acid recover ratio can attain as high as 66-72%. The recovered acid can be recycled to the back-extraction step by mixing it with high concentration acid and the waste recycled to the initial leaching stage by adjusting the acid concentration to recover valuable metal nickel and the residual acid. Therefore, the new technology discards nothing and shows many advantages whether in environmental aspect or economical aspect and thus should be deserved attention.

Anion Exchange Resins↗

In vitro androgenicity in pulp and paper mill effluents.

Pulp and paper mill effluents were examined for in vitro androgenicity using a recombinant yeast-based androgen receptor assay. Low levels of androgenic effects were detected in extracts of some effluents after activated sludge treatment. Yeast cell growth cell was inhibited in some samples, and this interfered with the androgenic response. Solid-phase fractionation revealed androgenicity after partial separation of components in the effluents. Comparison of levels in untreated effluent and in effluent treated in an aerated lagoon showed that this treatment had only a marginal effect on androgenicity. An assay of the fractions eluted with increasing concentrations of methanol showed that androgenic compounds were low to moderately lipophilic. In an attempt to identify these compounds, a number of wood-related compounds (guaiacol, vanillin, beta-sitosterol, betulin, pinosylvin-O-methyl ether, and a wood extract enriched in lignans) were examined but were found not to be androgenic. Raw process water was not androgenic, but water from a highly humified lake and process water from the production of pulp from partly decayed wood had low androgenicity. It therefore can be plausibly suggested that the androgens originated in decaying wood. An assay of androgenicity in the bile of juvenile rainbow trout exposed to effluents for 3 weeks showed increased dose-dependent levels of androgens after enzymatic hydrolysis of hormone conjugates.

Androgens↗

Fatal crashes involving young unlicensed drivers in the U.S.

INTRODUCTION: Young unlicensed drivers' involvement in fatal crashes is a recurrent problem in the United States. METHODS: This descriptive study extracted cross-sectional data on fatal crashes from the Fatality Analysis Reporting System from 1998 to 2002. Young unlicensed driver fatal crashes are examined by age, gender, and region. RESULTS: There were 2,452 young unlicensed driver fatal crashes representing 10.8% of all young drivers' fatal crashes. By age, 72.5% are over 15 years, males are involved in 74.5%, and southern and western states have a higher percent of young unlicensed driver fatal crashes. CONCLUSIONS: Subgroups of young people based on their age, gender, and region are over-represented in fatal crashes as unlicensed drivers. Further studies are needed to investigate the context and factors of young unlicensed drivers, essential to tailor interventions. IMPACT ON INDUSTRY: Young unlicensed drivers circumvent the established licensing process and pose a serious threat to themselves and other road users.

Accidents, Traffic↗

SPME in environmental analysis: biotransformation pathways.

Solid-phase microextraction (SPME) is an organic solvent-free sample preparation tool suitable for direct adsorption of analytes from the headspace or the aqueous phase of a matrix followed by desorption into a gas chromatograph (GC) or high-performance liquid chromatograph (HPLC) for subsequent analysis. The SPME technique is designed to accommodate the use of fibers coated with different polymers suitable for the extraction of chemicals with varied hydrophobic and polar properties. Also, the technique can minimize interference from other artefacts associated with complex samples, such as those encountered in biological matrices or reaction mixtures. The preceding characteristics of SPME make the technique suitable for real-time measurements of intermediate reaction products and, thus, able to provide insight into the fate of target chemicals and their degradation pathways. In the present article, the current state of knowledge on the use of SPME-GC and SPME-HPLC in the determination of frequently encountered environmental chemicals and their (bio)transformation pathways are critically reviewed. Future opportunities of SPME in real time in situ process monitoring such as the use of agricultural feed stocks to bio-based industrial products termed henceforth "process analytical chemistry" are also discussed.

Biotransformation↗