Computational aided acetaminophen - phthalic acid molecularly imprinted polymer design for analytical determination of known and new developed recreational drugs.

In recent times, abuse drug consumption rates have been increasing. In addition, authorities have detected a trend in the development of new substances expressly created to avoid legislation. These novel psychoactive substances (NPS) are non-registered formulations, closely chemically related to outlawed ones to maintain the same psychotropic effects while circumventing legal restrictions. This issue arises enormous social, sanitary, and road safety problems since there is no way to detect nor quantify these non-registered substances. The aim of this work is the development of a high selective material able to pre-concentrate and detect NPS. On that account, molecularly imprinted polymers (MIPs) designed with an imprinted cavity that matches the cathinones structural shape were proposed to detect both conventional and new cathinone derived recreational drugs. The increasing number of illicit drug modifications that is being reported requires developing a receptor valid for not only known molecules but also for incoming ones; thus, a virtual procedure must be carried out to take a step forward towards future modifications. Accordingly, a computational MIP design is proposed as the most appropriated method to effectively design this receptor. By means of molecular dynamics and molecular docking, several combinations are studied regarding their pre-polymerization complex stability but also their rebinding capacity against the proposed analytes. Hence, a phthalic acid - acetaminophen MIP is selected as the most well-suited receptor, valid for current and forthcoming cathinone recreational drugs.

Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study.

BACKGROUND: Lurbinectedin (PM01183) has synergistic antitumor activity when combined with doxorubicin in mice with xenografted tumors. This phase I trial determined the recommended dose (RD) of doxorubicin (bolus) and PM01183 (1-h intravenous infusion) on day 1 every 3 weeks (q3wk), and obtained preliminary evidence of antitumor activity for this combination in small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with advanced solid tumors received doxorubicin and PM01183 following a standard dose escalation design and expansion at the RD. Twenty-seven patients had relapsed SCLC: 12 with sensitive disease (platinum-free interval ≥90 days) and 15 with resistant disease (platinum-free interval <90 days). RESULTS: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose was the RD. In relapsed SCLC, treatment tolerance at the RD was manageable. Transient and reversible myelosuppression (including neutropenia, thrombocytopenia, and febrile neutropenia) was the main toxicity, managed with dose adjustment and colony-stimulating factors. Fatigue (79%), nausea/vomiting (58%), decreased appetite (53%), mucositis (53%), alopecia (42%), diarrhea/constipation (42%), and asymptomatic creatinine (68%) and transaminase increases (alanine aminotransferase 42%; aspartate aminotransferase 32%) were common, and mostly mild or moderate. Complete (n = 2, 8%) and partial response (n = 13, 50%) occurred in relapsed SCLC, mostly at the RD. Response rates at second line were 91.7% in sensitive disease [median progression-free survival (PFS)=5.8 months] and 33.3% in resistant disease (median PFS = 3.5 months). At third line, response rate was 20.0% (median PFS = 1.2 months), all in resistant disease. CONCLUSION: Doxorubicin 50 mg/m2 and PM01183 4.0 mg flat dose on day 1 q3wk has shown remarkable activity, mainly in second line, with manageable tolerance in relapsed SCLC, leading to further evaluation of this combination within an ongoing phase III trial.

Methane potential and anaerobic treatment feasibility of Sargassum muticum.

The aim of this research was to study the feasibility of anaerobic digestion of the alga Sargassum muticum with special attention to its biodegradability, potential toxicity caused by its salt content, alga components and intermediate process compounds, and potential limitations to continuous treatment. Specific methane potential (SMP) for three samples of S. muticum collected from the Galician coast (Northwest Spain) at different seasons ranged from 166 to 208 mLCH4/gVS while accumulation of toxic compounds was not observed at alga concentrations of up to 100 gTS/L, except for one of the samples in which inhibition started at 80-100 gTS/L. Continuous digestion is feasible at alga concentration up to 100 gTS/L with methane production rates ranging from 0.14 to 0.26 LCH4/Ld at organic loading rates of 3.2 gTS/Ld, but SMP dropped to 113-159 mLCH4/gVS.

Selective removal of ATP degradation products from food matrices II: Rapid screening of hypoxanthine and inosine by molecularly imprinted matrix solid-phase dispersion for evaluation of fish freshness.

A water compatible molecularly imprinted polymer (MIP), synthesized using theophylline (TPH) as dummy-template and acrylamide (AM) as functional monomer, has been employed as supporting material in matrix solid-phase dispersion combined with ultra performance liquid chromatography-photodiode array detection (MSPD-UPLC-PDA) for selective determination of adenosine triphosphate (ATP) derivatives in fish samples. ATP degradation products are used as freshness index for assessment of fish quality. The solid sample was directly blended with MIP in MSPD procedure resulting in sample disruption and subsequent adsorption of the compounds on the MIP. By using n-hexane and ammonium hydroxide aqueous solution at pH 9 as the washing and elution solvent, respectively, satisfactory recoveries and clean chromatograms have been obtained. Good linearity for hypoxanthine (HYP) and inosine (INO) has been observed with correlation coefficients (R(2)) of 0.9987 and 0.9986, respectively. The recoveries of the two ATP derivatives at three different spiked levels ranged from 106.5% to 113.4% for HYP and from 103.1% to 111.2% for INO, with average relative standard deviations lower than 4.2% in both cases. This new method, which is rapid, simple and sensitive, can be used as an alternative tool to conventional tedious methods.

Molecularly imprinted polymer for selective determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid using LC-MS/MS in urine and oral fluid.

The use of molecularly imprinted polymers (MIPs) for solid phase extraction (MISPE) allows a rapid and selective extraction compared with traditional methods. Determination of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-Δ(9)-tetrahydrocannabinol carboxylic acid (THC-COOH) in oral fluid (OF) and urine was performed using homemade MISPEs for sample clean-up and liquid chromatography tandem mass spectrometry (LC-MS/MS). Cylindrical MISPE shaped pills were synthesized using catechin as a mimic template. MISPEs were added to 0.5 mL OF or urine sample and sonicated 30 min for adsorption of analytes. For desorption, the MISPE was transfered to a clean tube, and sonicated for 15 min with 2 mL acetone:acetonitrile (3:1, v/v). The elution solvent was evaporated and reconstituted in mobile phase. Chromatographic separation was performed using a SunFire C18 (2.5 µm; 2.1 × 20 mm) column, and formic acid 0.1% and acetonitrile as mobile phase, with a total run time of 5 min. The method was fully validated including selectivity (no endogenous or exogenous interferences), linearity (1-500 ng/mL in OF, and 2.5-500 ng/mL in urine), limit of detection (0.75 and 1 ng/mL in OF and urine, respectively), imprecision (%CV <12.3%), accuracy (98.2-107.0% of target), extraction recovery (15.9-53.5%), process efficiency (10.1-46.2%), and matrix effect (<-55%). Analytes were stable for 72 h in the autosampler. Dilution 1:10 was assured in OF, and Quantisal™ matrix effect showed ion suppression (<-80.4%). The method was applied to the analysis of 20 OF and 11 urine specimens. This is the first method for determination of THC and THC-COOH in OF using MISPE technology.

Synthesis and characterization of bisphenol-A imprinted polymer as a selective recognition receptor.

Molecularly imprinted polymers (MIPs) are currently used to provide selectivity in chemical sensors. In this context, a non-covalent bisphenol-A (BPA)-imprinted polymer using 4-vinylpyridine (4-Vpy) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as crosslinker and a low volatile solvent, triethylene glycol dimethyl ether (TRIGLYME), in combination with a non-reactive linear polymer, poly (vinyl acetate) (PVAc), as porogen, was synthesized with a simple polymerization procedure. Batch rebinding experiments were carried out to evaluate the binding and selectivity properties of the BPA-MIP. The experimental adsorption isotherms were fitted and a heterogeneous distribution of the binding sites was found. The selectivity of MIP demonstrated higher affinity for target BPA and BPA-analogues over other common water pollutants. The adsorption kinetics followed the pseudo-second-order kinetic model so that the specific adsorption in the imprinted cavities by two strong hydrogen bonds could be described as a chemisorption process. The diffusion mechanism was determined by the intra-particle diffusion and Boyd models, both of them revealing that the adsorption was mainly governed by intra-particle diffusion. MIP was shown to be promising for regeneration without significant loss in adsorption capacity.

Effect of several variables in the polymer toys additive migration to saliva.

Capacity to migrate of a representative group of polymeric additives, dyes, antioxidants, hindered amine light stabilizers (HALS) or antistatics, from plastic toys to saliva was analyzed to protect children in their habits of sucking and biting. Most of target additives appear no-regulated in toys normative but adverse effects on human health of some of them have been demonstrated and their presence in others commercial articles normative has been included. In order to offer an effective and easy tool to perform these controls, migration tests by dynamic and static contact, followed by a preconcentration step by liquid-liquid extraction (LLE) and ultra performance liquid chromatographic analysis with ultraviolet-visible and evaporative light scattering detections (UPLC-UV/Vis-ELSD) have been optimized to evaluate the migrated amounts of the additives in saliva simulant. The detection limits of the migration methodologies were ranged from 8.68 × 10(-2) to 1.30 × 10(-3)mg migrated (L simulant)(-1). Influence of several variables on this mass transport, as time, temperature and friction, was also analyzed to achieve the most aggressive methodology to protect consumers. Migration of several studied additives, whose presence has been demonstrated in several purchased commercial toys, has been observed.

MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.

BACKGROUND: Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target. METHODS: To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed. RESULTS: In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a multivariate analysis. CONCLUSIONS: MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease.

Liquid chromatography method to determine polyamines in thermosetting polymers.

A simple, robust and sensitive analytical method to determine three polyamines commonly used as hardeners in epoxy resin systems and in the manufacture of polyurethane is reported. The studied polyamines are: one tetramine, TETA (triethylenetetramine), and two diamines, IPDA (Isophorone diamine) and TCD-diamine (4,7-methano-1H-indene-5,?-dimethanamine, octahydro-). The latter has an incompletely defined structure, and, as far as we know, has not been previously determined by other methods. All three polyamines contain primary amines; TETA also contains secondary amines. The analytical method involves derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate, used for the first time for these compounds, followed by high performance liquid chromatography (HPLC) analysis with a fluorescence (FL) detector (lambda excitation 248nm, lambda emision 395nm). The HPLC-DAD-LTQ Orbitrap MS was used in order to provide structural information about the obtained derivatized compounds. The hybrid linear ion trap LTQ Orbitrap mass spectrometer has been introduced in recent years and provides a high mass accuracy. The structures of the derivatized analytes were identified from the protonated molecular ions [M+H](+) and corresponded to the fully labelled analytes. The following analytical parameters were determined for the method using the HPLC-FL: linearity, precision (2.5-10%), instrumental precision intraday (0.8-1.5%) and interday (2.9-6.3%), and detection limits (0.02-0.14mgL(-1)). The stability of stock solutions and derivatized compounds was also investigated. The method was applied to determine the amine free content in epoxy resin dust collected in workplaces.

High-performance liquid chromatography analysis of ten dyes for control of safety of commercial articles.

Two high-performance liquid chromatographic methods, with ultraviolet-visible spectrophotometry detection (HPLC-UV/Vis) and with tandem mass spectrometry triple quadrupole interfaced with positive ion mode electrospray ionization detection (HPLC-ESI+-QqQ-MS/MS), for determination and quantification of ten commercial dyes are proposed for control in commercial products. Multiple peaks observed for some of the studied dyes in HPLC-UV/Vis chromatograms forced to obtain structural information by HPLC-ESI-MS/MS method with scan mode. The quality parameters of the two proposed chromatographic methods were evaluated for different requirements of normative, showing detection (LODs) and quantification (LOQs) limits around 60-890 and 200-2990 microg L(-1) for HPLC-UV/Vis, and 4.54-14.3 and 15.0-47.6 microg L(-1) for HPLC-ESI+-QqQ-MS/MS.

Antioxidant content of and migration from commercial polyethylene, polypropylene, and polyvinyl chloride packages.

Antioxidants commonly used in polyolefins were studied in commercial food packages made of low- and high-density polyethylene (LDPE and HDPE), polypropylene (PP), polyvinylchloride (PVC), and polyethylene terephtalate (PET) and in a LDPE film extruded at the laboratory. The phenolic antioxidants BHA, BHT, AO 2246, AO 425, Ethanox 330, Irganox 1010, and Irganox 1076 were studied together with the phosphite Irgafos 168 and their two degradation products, phosphate and DBP. Antioxidants were extracted from polyolefins using microwave energy and analyzed using high-performance liquid chromatography (HPLC) to determine the antioxidant content in the diverse commercial films. Irganox 1010 and Irganox 1076 were found in the majority of the samples generally together with the phosphite Irgafos 168 and its oxidized product (phosphate). Specific migration levels of each antioxidant were determined by HPLC after pretreatment with solid-phase extraction (SPE) in aqueous food simulants and after their dilution with tetrahydrofuran (THF) in fatty food simulant. These levels were much lower than limits allowed by legislation.

Determination of antioxidants by solid-phase extraction method in aqueous food simulants.

An analytical method for the determination of specific migration levels of phenolic antioxidants and one phosphite antioxidant in the aqueous food simulants established by European legislation has been developed. This method involves solid-phase extraction (SPE) of the antioxidants with silica C(18) cartridge and their determination by liquid chromatography (LC) with diode-array detection. The achieved results in the studies of elution volume determination, breakthrough volume and accuracy are showed. Recoveries in the range of 78-104% and a relative standard deviation between 2.0 and 7.7% have been achieved.

Diferencias clínicas en la depresión según la clase social / Clinical differences in depression according to social class

Los objetivos del estudio fueron: a) determinar si había diferencias en la semiología depresiva según la clase social (CS); b) averiguar si estas diferencias, en caso de existir, se debían fundamentalmente a la CS o más bien a otras variables clínicas o sociodemográficas. Se estudiaron 140 pacientes ambulatorios de Galicia con el CET-DE, el 61 por ciento rurales, diagnosticados de depresión según criterios DSM-III-R. Se elaboró una escala de CS a partir de la ocupación del cabeza de familia, los ingresos familiares y los estudios del paciente. Los pacientes de los niveles inferiores de CS referían con mayor frecuencia síntomas físicos y ansiedad; y los de las superiores, deterioro cognitivo y culpa. En el análisis logístico se observó que las variables socioeconómicas y la residencia eran las que en mayor medida explicaban estas diferencias (AU)

First assessment of dioxin emissions from coal-fired power stations in Spain.

In this work, the findings of the first assessment of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in emissions releases to the atmosphere from coal-fired power plants are given. A total of five plants were selected for the study located at different provinces in Spain. In all the cases, the results revealed very low levels, in the range of 0.41 pg I-TEQ/Nm(3). The profile indicated in the majority of the cases predominance of highly chlorinated congeners being OCDD the most important contributor. The findings were also used to estimate contribution of PCDDs/PCDFs emitted from coal-fired power plants in Spain. Individual plant results revealed values below 0.02 g I-TEQ per year and plant. Nevertheless, considering the total coal consumption in Spain in 1997, the values are comparable to those reported in other countries in the range of 0.6-0.7 g I-TEQ per year. Moreover, emission factors were determined considering operating conditions of evaluated plants. In general, large variability was observed and values below 1-5 pg I-TEQ/kg coal were early reached.

Nuevos modelos de gestión hospitalaria: encuesta a los gerentes de grandes centros hospitalarios / New hospital management models: survey of large hospital center managers

En este artículo se afronta el debate sobre nuevos modelos de gestión hospitalaria. Se ha utilizado una triple metodología: análisis de fuentes secundarias, entrevistas a fondo y reuniones de grupo, y una encuesta a gerentes de centros hospitalarios con 400 camas o más. Principales resultados: Hay una gran consistencia y complementariedad en las aportaciones de estas 3 vías. Las nuevas formas jurídico-administrativas de gestión, así como las áreas de gestión clínica, comienzan a abrirse camino en estos hospitales con lentitud; los gerentes demandan mayor autonomía en la gestión y apuestan por la profesionalización de la gerencia a partir de una formación específica (AU)

Determination of antioxidant migration levels from low-density polyethylene films into food simulants.

An analytical method for the determination of specific migration levels of phenolic antioxidants from low-density polyethylene (LDPE) into food simulant has been developed. The screening and response surface experimental designs to optimize the liquid-liquid extraction (LLE) of these antioxidants have been tested and the analyses have been carried out by reversed-phase high-performance liquid chromatography (HPLC) coupled with ultraviolet diode-array detector. The procedure developed has been applied to specific migration tests in different commercial LDPE films. The considered antioxidants have not been found upper the legislation limits although Ethanox 330 and Irgafos 168 have been found at trace level.

Behavior of fluorine and chlorine in Spanish coal fired power plants with pulverized coal boilers and fluidized bed boiler.

Behavior and contents of fluorine and chlorine in coal feedstock, combustion wastes (slag and fly ash) and emissions were studied in five conventional coal fired power plants and in a fluidized bed coal power plant. The halide levels found in the used coal were quite low. Mass balances and emission factors were calculated. The volatility of these elements makes the gaseous emission the main target between the residues. The influence of combustion parameters is not clearly established. Several analytical techniques (ion selective electrodes, capillary electrophoresis and ion chromatography) are employed to determinate the halide concentration in the different samples taken in the power plants studied (coal, slag, fly ash and flue gases).

Determination of chlorotriazines, methylthiotriazines and one methoxytriazine by SPE-LC-UV in water samples.

Triazine herbicides form a wide group of substances that belong among the most common agrochemicals applied for pre- and post-emergence weed control. So, they can be found in the environment at trace level. In order to determine their concentrations in water samples by the usual analytical techniques, a preconcentration step is commonly necessary. In this paper, a simple analytical method for the quantification of eight triazines (three chlorotriazines, four methylthiotriazines and one methoxytriazine) in water samples by solid phase extraction-reversed phase liquid chromatography (LC) has been developed. LC shows good analytical performance for simultaneous multiple triazine analysis (repeatability <2%, reproducibility <3%), except for prometon (repeatability 5.52%, reproducibility 16%). The results, obtained by using carbograph and polymeric sorbents for solid phase extraction (SPE), have been compared. The limits of quantification achieved permit the application of the proposed SPE-LC method for the determination of eight triazines in water samples (0.0065-0.028 mug l(-1)).

Propuesta de una escala de clase social destinada a pacientes con depresión / Proposal of a social class scale destined to depresive patients

Se elaboró una escala de cinco niveles de clase social con la ocupación del cabeza de familia, el nivel de estudios del paciente y los ingresos familiares. Los objetivos del estudio fueron determinar si la clase social elaborada es representativa de los factores socioeconómicos y útil para el estudio de las diferencias clínicas en pacientes con depresión en Galicia.Se estudiaron 140 pacientes diagnosticados de depresión (DSM-III-R), 60,7 por ciento del medio rural. La escala de clase social se asoció de forma significativa con todas las variables e indicadores socioeconómicos (p <0,001), excepto con la proporción entre dormitorios y personas.La clase social elaborada y los estudios, fueron las variables con las que mayores diferencias clínicas se apreciaron.La escala de clase social elaborada cumplió los objetivos para los que fue diseñada. Al estudiar la clase social en pacientes con depresión es preferible utilizar una escala multidimensional (AU)

Determination of volatile organic compounds in emissions by coal-fired power stations from Spain.

This study concerns the emissions of volatile organic compounds (VOCs) by coal fired power stations. The main compounds are monoaromatic hydrocarbons and aliphatic hydrocarbons, chlorinated compounds have less importance. The influence of combustion parameters can not be clearly established. Emissions factors were calculated and they are smaller than those of other anthropogenic combustions. A comparative study of two sources of VOCs, power stations and motor vehicles, indicates that the environmental impact of the latter are most important.