607 research outputs found
Screening the Pathogen Box for Identification of New Chemical Agents with Anti-Fasciola hepatica Activity
Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 mu M each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC(50)s of 50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 mu M; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted
Prediction of Zamorano cheese quality by near-infrared spectroscopy assessing false non-compliance and false compliance at minimum permitted limits stated by designation of origin regulations
Near-infrared transmittance (NIT) spectroscopy was used to predict the percentage in weight of the fat, dry matter, protein and fat/dry matter contents in Zamorano cheeses, protected with a Designation of Origin by the European Union. A total of 42 cheeses submitted to official control were analysed by reference methods. Samples were scanned (850–1050 nm) and predictive equations were developed using Partial Least Squares regression with a cross-validation step. Eight pretreatments independent from the remaining calibration samples were first considered. The most adequate one was that performing the second derivative (using a Savitzky–Golay method with a nine-point window and a second-order polynomial) followed by the standard normal variate transformation. Percentages of the root mean square error in cross-validation, the coefficient of determination and the mean of the absolute value of relative errors found were, respectively, for fat (0.62; 96.16; 1.05), dry matter (0.76; 96.03; 0.83), protein (0.41; 97.82; 0.81) and the fat/dry matter ratio (0.61; 92.51; 0.66). At a 99% confidence level, the trueness of the NIT+PLS methods for fat, dry matter and protein was verified. The official regulation for Zamorano cheese demands minimum permitted limits on the percentages in weight for protein (25%), dry matter (55%) and the ratio of fat to dry matter (45%). The adaptation of both the decision limit and the detection capability to the case of a minimum permitted limit (CDα and CDβ, respectively) when a Partial Least Squares calibration is used has been applied for the first time for a food product protected by a Designation of Origin. The values of CDα with a probability of false non-compliance equal to 0.05 and of CDβ when, in addition, the probability of false compliance was equal to or less than 0.05, both provided by the corresponding NIT+PLS-based method, were, respectively, for protein (24.78%; 24.57%), dry matter (54.14%; 53.28%) and the fat/dry matter ratio (44.39%; 43.78%).authorsthankthefinancialsupportprovidedbyMinisterio
de CienciaeInnovacio´n (CTQ2011-26022)andJuntadeCastillay
Leo´n (BU108A11-2
Identification and quantification of carbamate pesticides in dried lime tree flowers by means of excitation-emission molecular fluorescence and parallel factor analysis when quenching effect exists
A non-separative, fast and inexpensive spectrofluorimetric method based on the second order calibration of excitation-emission fluorescence matrices (EEMs) was proposed for the determination of carbaryl, carbendazim and 1-naphthol in dried lime tree flowers. The trilinearity property of three-way data was used to handle the intrinsic fluorescence of lime flowers and the difference in the fluorescence intensity of each analyte. It also made possible to identify unequivocally each analyte. Trilinearity of the data tensor guarantees the uniqueness of the solution obtained through parallel factor analysis (PARAFAC), so the factors of the decomposition match up with the analytes. In addition, an experimental procedure was proposed to identify, with three-way data, the quenching effect produced by the fluorophores of the lime flowers. This procedure also enabled the selection of the adequate dilution of the lime flowers extract to minimize the quenching effect so the three analytes can be quantified. Finally, the analytes were determined using the standard addition method for a calibration whose standards were chosen with a D-optimal design.
The three analytes were unequivocally identified by the correlation between the pure spectra and the PARAFAC excitation and emission spectral loadings. The trueness was established by the accuracy line “calculated concentration versus added concentration” in all cases. Better decision limit values (CCα), in x0 = 0 with the probability of false positive fixed at 0.05, were obtained for the calibration performed in pure solvent: 2.97 μg L−1 for 1-naphthol, 3.74 μg L−1 for carbaryl and 23.25 μg L−1 for carbendazim. The CCα values for the second calibration carried out in matrix were 1.61, 4.34 and 51.75 μg L−1 respectively; while the values obtained considering only the pure samples as calibration set were: 2.65, 8.61 and 28.7 μg L−1, respectively.theMinisteriodeEconomíayCompetitividad(CTQ2011-26022)
and JuntadeCastillayLeón(BU108A11-2
Correction des biais des mesures de pluie du satellite CMORPH à l'aide de données observées sur Bogotá, Colombie
Determination of dichlobenil and its major metabolite (BAM) in onions by PTV–GC–MS using PARAFAC2 and experimental design methodology
The optimization of a GC–MS analytical procedure which includes derivatization, Quick Easy Cheap Effective Rugged and Safe (QuEChERS) and programmed temperature vaporization (PTV) using design of experiments is performed to determine 2,6-dichlorobenzonitrile (dichlobenil) and 2,6-dichlorobenzamide (BAM) in onions, using 3,5-dichlorobenzonitrile and 2,4-dichlorobenzamide as internal standards. The use of a central composite design and two D-optimal designs, together with the desirability function, makes it possible to significantly reduce the economic, time and environmental cost of the study. The usefulness of PARAFAC2 for solving problems as the interference of unexpected derivatization artifacts unavoidably linked to some derivatization agents, or the presence of coeluents from the complex matrix, which share m/z ratios with the target compounds, is shown. The limits of decision (CCα) of the optimized procedure, 5.00 μg kg− 1 for dichlobenil and 1.55 μg kg− 1 for BAM (α = 0.05), are below the maximum residue limit (MRL) established by the EU for dichlobenil (20 μg kg− 1) in this commodity.Ministerio de Economía y Competitividad (CTQ2011-26022) and Junta
de Castilla y León (BU108A11-2
Standard addition method based on four-way PARAFAC decomposition to solve the matrix interferences in the determination of carbamate pesticides in lettuce using excitation–emission fluorescence data
The simultaneous determination of two carbamate pesticides (carbaryl and carbendazim) and of the degradation product of carbaryl (1-naphthol) in iceberg lettuce was achieved by means of PARAFAC decomposition and excitation–emission fluorescence matrices. A standard addition method for a calibration based on four-way data was applied using different dilutions of the extract from iceberg lettuce as a fourth way that provided the enough variation of the matrix to carry out the four-way analysis. A high fluorescent overlapping existed between the three analytes and the fluorophores of the matrix. The identification of two fluorescent matrix constituents through the four-way model enabled to know the matrix contribution in each dilution of the extract. This contribution was subtracted from the previous signals and a subsequent three-way analysis was carried out with the tensors corresponding to each dilution. The PARAFAC decomposition of these resulting tensors showed a CORCONDIA index equal to 99%. For the identification of the analytes, the correlation between the PARAFAC spectral loadings and the reference spectra has been used. The trueness of the method, in the concentration range studied, was guaranteed because there was neither constant nor proportional bias according to the appropriate hypothesis tests. The best recovery percentages were obtained with the data from the most diluted extract, being the results: 127.6% for carbaryl, 125.55% for carbendazim and 87.6% for 1-naphthol. When the solvent calibration was performed, the decision limit (CCα) and the capability of detection (CCβ) values, in x0=0, were 2.21 and 4.38 μg L−1 for carbaryl, 4.87 and 9.64 μg L−1 for carbendazim; and 3.22 and 6.38 μg L−1 for 1-naphthol, respectively, for probabilities of false positive and false negative fixed at 0.05. However, these values were 5.30 and 10.49 μg L−1 for carbaryl, 18.05 and 35.73 μg L−1 for carbendazim; and 1.92 and 3.79 μg L−1 for 1-naphthol, respectively, when the matrix-matched calibration using the most diluted extract was carried out in the recovery study.Ministerio de Economía y Competitividad(CTQ2011-26022)
and JuntadeCastillayLeón(BU108A11-2)
New molecular approaches in adipogenesis regulation: The connexin 43 role
Indexación: Scopus; Redalyc.La prevalencia de la obesidad a nivel mundial se ha incrementado
rápidamente durante los últimos años debido principalmente
a los cambios en el estilo de vida de la población
con un aumento significativo en el consumo de energía y disminución
de los niveles de actividad física. Es por esto que
la comunidad científica está interesada en comprender de
forma más profunda los mecanismos que regulan la fisiopatología
de la obesidad. Dentro de los diferentes blancos de
estudio se encuentra la adipogénesis, cuyo entendimiento es
fundamental para comprender el desarrollo de la obesidad y
las patologías asociadas a esta. Recientemente ha surgido
importantes evidencias que involucran a la proteína de canales
de “Gap Junction” conexina 43 (Cx43) en la regulación
de los procesos relacionados con adipogénesis, cuyo papel
es básicamente anti-adipogénico, sin embargo, nuevas funciones
de Cx43 en la regulación de la formación del tejido
adiposo siguen descubriéndose.The global prevalence of obesity has been increased rapidly
over the past few years mainly due to changes in the lifestyle
of the population with a significant increase in energy
consumption and decreased levels of physical activity. As a
result, the scientific community is interested in a deeper understanding
of the mechanisms that regulate the pathophysiology
of obesity. In this context, adipogenesis process is an
important target of study to understand the obesity and associated
pathologies. Recently has been emerged important
evidence that involve gap junction channel protein connexin
43 (Cx43) in the regulation of processes related to adipogenesis,
whose role is fundamentally anti-adipogenic. However,
new functions of Cx43 in the regulation of adipose tissue
function also continued to emerge.http://www.redalyc.org/articulo.oa?id=5594990800
FTO gene: Historic background and its relationship with chronic-degenerative diseases
Indexación: Scopus; Latindex.Alteraciones en el desarrollo de la atención
y la organización conductual pueden
configurar cuadros clínicos como
el trastorno déficit de atención (TDA) que puede estar
acompañado o no de hiperactividad (TDAH), este último
parece tener una relación directa con otros diagnósticos
de tipo endocrino como la obesidad. El objetivo del estudio
es analizar la relación que existe entre el TDAH y la
obesidad. Es por ello que se realiza una revisión sistemática
de estudios científicos revelando relaciones y diferencias
entre ambos trastornos desde una mirada fisiológica,
cognoscitiva y comportamental. Se concluye que la relación
entre el TDAH y la obesidad se da por factores genéticos,
por variaciones dopaminérgicas, cambios en patrones
de sueño, desajustes emocionales y por alteraciones en la
regulación de la conducta; igualmente influyen factores
sociales relacionados con el cuidado en el embarazo y la
alimentación de las mujeres antes y durante la gestación.http://www.revhipertension.com/rlh_2_2018/5_fto_gene.pd
Effect of Helicobacter pylori infection and acid blockade by lansoprazole on clarithromycin bioavailability
Robustness testing in the determination of seven drugs in animal muscle by liquid chromatography–tandem mass spectrometry
In this work, the robustness of the sample preparation procedure for the determination of six tranquilizers (xylazine, azaperone, propionylpromazine, chlorpromazine, haloperidol, and azaperol) and a beta-blocker (carazolol) in animal muscle by LC/MS–MS was assessed through the experimental design methodology. A 2III7 − 4 fractional factorial design was performed to evaluate the influence of seven variables on the final concentration of the seven drugs in the samples, in accordance with what is laid down in Commission Decision No 2002/657/EC. The variation considered for each of those seven factors is likely to happen when preparing the samples, being the values chosen as level − 1, the nominal operating conditions. The results of the experimentation were evaluated from different statistical strategies, such as hypothesis testing using an external variance previously estimated, Lenth's method, and Bayesian analysis. Both Lenth's and Bayes' approaches enabled to determine the effect of every variable even though no degrees of freedom were left to estimate the residual error. The same conclusion about the robustness of the extraction step was reached from the three methodologies, namely, none of the seven factors examined influenced on the method performance significantly, so the sample preparation procedure was considered to be robust.Ministerio de
Ciencia e Innovación (CTQ2011-26022) and MINECO (CTQ2014-
53157-R)
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