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1.
Rev. toxicol ; 40(1): 40-44, ene.-jun. 2023. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-222866

RESUMO

Las aves marinas pueden ser utilizadas como bioindicadoras de las alteraciones del ambiente en que residen, identificándose en ellas distintos biomarcadores, que no informen sobre los niveles cuantitativos de contaminantes sino sobre los efectos adversos subclínicos que dichos agentes pueden causar. En el presente trabajo se han analizado los niveles de Malondialdehído (MDA) y de actividad Glutatión-S-Transferasa (GST) en muestras de hígado y riñón de 30 alcatraces (Morus bassanus) procedentes de las costas de Galicia, como posibles indicadores de estrés oxidativo en las aves. Además, se ha determinado la influencia de dos factores endógenos (sexo y edad) sobre los niveles de estos biomarcadores. En hígado los valores medios de MDA obtenidos fueron de 0,508±0,502 nmol/mg proteína, mientras que en riñón fueron de 15,67±12,18 nmol/mg proteína. La actividad GST media en hígado fue de 10,93±7,067 nmol/min/mg proteína, mucho menor que la media de los valores en riñón, que fue 62,30±26,97 nmol/min/mg proteína. En cuanto a las variaciones respecto a la edad, solo se encontraron diferencias estadísticamente significativas en riñón en la actividad GST, siendo mayor la actividad de esta enzima en alcatraces adultos que en inmaduros. Por su parte, el factor sexo no influyó en los niveles de ninguno de los biomarcadores considerados. Los resultados obtenidos apuntan a que ambos biomarcadores podrían ser de utilidad en programas de biomonitorización de contaminación ambiental centrados en el alcatraz, aunque serían necesarios estudios que consideren un mayor número de animales, incorporando un abanico más amplio de biomarcadores. (AU)


Seabirds can be used as bioindicators of changes in the environment in which they live, identifying different biomarkers in them, which do not provide information on the quantitative levels of contaminants, but on the subclinical adverse effects that these agents can cause. At the present study, the levels of Malondialdehyde (MDA) and glutathione-S-transferase (GST) activity in liver and kidney samples of 30 gannets (Morus bassanus) from the coast of Galicia have been determined, as suitable biomarkers of oxidative stress on birds. In addition, the influence of two endogenous factors (sex and age) on the levels of these biomarkers has been determined. In the liver, the mean values of MDA were 0.508 ± 0.502 nmol/mg protein, while in kidney they were 15.67 ± 12.18 nmol/mg protein. On the other hand, mean GST activity in the liver was 10.93 ± 7.067 nmol/min/mg protein, much lower than the mean activity values found in kidney, which were 62.30 ± 26.97 nmol/min/mg protein. Regarding the variations with respect to age, statistically significant differences were only found in the kidney in GST activity, the activity of this enzyme being higher in adult gannets than in immature ones. Secondly, the gender factor did not influence the levels of any of the biomarkers considered. The obtained results indicate that both biomarkers could be useful in biomonitoring programs of environmental contamination focused on the gannet, although studies that consider a larger number of animals, incorporating a broader range of biomarkers, would be necessary. (AU)


Assuntos
Animais , Morus , Biomarcadores , Estresse Oxidativo , Espanha , Malondialdeído , Glutationa Transferase , Aves
2.
Nat Commun ; 13(1): 2912, 2022 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-35614049

RESUMO

The primary steps of photosynthesis rely on the generation, transport, and trapping of excitons in pigment-protein complexes (PPCs). Generically, PPCs possess highly structured vibrational spectra, combining many discrete intra-pigment modes and a quasi-continuous of protein modes, with vibrational and electronic couplings of comparable strength. The intricacy of the resulting vibronic dynamics poses significant challenges in establishing a quantitative connection between spectroscopic data and underlying microscopic models. Here we show how to address this challenge using numerically exact simulation methods by considering two model systems, namely the water-soluble chlorophyll-binding protein of cauliflower and the special pair of bacterial reaction centers. We demonstrate that the inclusion of the full multi-mode vibronic dynamics in numerical calculations of linear spectra leads to systematic and quantitatively significant corrections to electronic parameter estimation. These multi-mode vibronic effects are shown to be relevant in the longstanding discussion regarding the origin of long-lived oscillations in multidimensional nonlinear spectra.


Assuntos
Clorofila , Complexos de Proteínas Captadores de Luz , Clorofila/química , Eletrônica , Transferência de Energia , Complexos de Proteínas Captadores de Luz/metabolismo , Proteínas , Análise Espectral/métodos
3.
Rev. toxicol ; 38(1): 8-11, 2021. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-230700

RESUMO

La creciente preocupación por el bienestar animal ha propiciado el rechazo por parte de la sociedad a la utilización de animales en experimentación. Por este motivo, actualmente se están desarrollando métodos alternativos que cumplan con el principio de las 3Rs (reemplazar, reutilizar y refinar). Muchos de estos métodos se basan en la utilización de organismos inferiores, como las lombrices de tierra. El presente estudio desarrolla el ensayo estandarizado de la Organización Internacional de Normalización (ISO) 17512-1:2008, en el que se evalúa la toxicidad producida por el plaguicida organofosforado dimetoato en el suelo, utilizando la capacidad de repulsión o evitación que presentan las lombrices de tierra pertenecientes a la especie Aporrectodea caliginosa. Las concentraciones seleccionadas han sido 0,06, 0,3 y 1,5 mg/kg de suelo, ensayada cada una de ellas por triplicado, empleando 10 lombrices por cada réplica. Los resultados reflejan la capacidad de las lombrices de tierra de la especie Aporrectodea caliginosa para evitar suelos contaminados con el formulado comercial de dimetoato. Por otra parte, se confirma la tendencia de las lombrices a evitar el suelo contaminado a medida que aumenta la concentración de plaguicida ensayada, con significación estadística a la dosis más alta empleada (1,5 mg/kg). (AU)


The increasing concern about animal wellness has induced the repulse of society to the use of animals in research. For this reason, alternative methods which comply with the 3Rs principle (Replace, Reuse and Refine) are currently being developed. Many of these methods are based on the use of lower organisms on the evolutionary scale, such as earthworms. The present study develops the standardized test of the International Organization of Standardization (ISO) 17512-1:2008, in which the toxicity produced by the pesticide organophosphate dimethoate in the soil is evaluated, using the capacity of repulsion or avoidance that presents the earthworms Aporrectodea caliginosa. The assayed concentrations were 0.06, 0.3 and 1.5 mg/kg of soil, each one tested in triplicated, using 10 earthworms for each repetition. The results reflect the ability of earthworms of the species Aporrectodea calliginosa to avoid soils contaminated with the commercial formulation of dimethoate. On the other hand, the tendency of worms to avoid contaminated soils is confirmed as the concentration of pesticide increases, with statistical significance at the highest concentration used (1.5 mg/kg). (AU)


Assuntos
Animais , Poluição Ambiental , Qualidade do Solo , Dimetoato/efeitos adversos , Dimetoato/toxicidade , Inseticidas Organofosforados , Oligoquetos
4.
Rev. toxicol ; 38(2): 84-88, 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-230709

RESUMO

En la primera parte del presente estudio, publicado en 2021, se mostraron los resultados obtenidos al aplicar el ensayo estandarizado de la Organización Internacional de Normalización (ISO) 17512-1:2008. En dicho trabajo se evaluó la toxicidad producida por el plaguicida organofosforado dimetoato en el suelo, utilizando la capacidad de repulsión o evitación que presentan las lombrices de tierra de la especie Aporrectodea caliginosa. En esta segunda parte, para evaluar los efectos subletales producidos por el dimetoato sobre las lombrices, se han determinado como biomarcadores la actividad de la enzima acetilcolinesterasa (AChE, cuya inhibición es el principal mecanismo de acción de este tipo de compuestos) y la actividad glutatión S-transferasa (GST, que comúnmente se activa como mecanismo de detoxificación de plaguicidas). Las concentraciones seleccionadas han sido 0,06, 0,3 y 1,5 mg/kg de suelo, ensayada cada una de ellas por triplicado, empleando 10 lombrices por cada réplica.La actividad AChE se inhibió significativamente en la exposición a las tres concentraciones empleadas. No se ha producido aumento de la actividad GST que, por el contrario, aparece significativamente inhibida a la concentración más alta de plaguicida ensayada. La falta de una inducción de la actividad GST puede deberse a que el mecanismo de detoxificación no se ha puesto en marcha por el corto tiempo de exposición al plaguicida. Estos resultados reflejan la sensibilidad de la AChE como biomarcador de la contaminación de los suelos con organofosforados. (AU)


In the first part of this study, published in 2021, the results obtained when applying the standardized test of the International Organization of Standardization (ISO) 17512-1:2008 were shown. In this study, the toxicity produced by the pesticide organophosphate dimethoate in the soil was evaluated, using the capacity of repulsion or avoidance that presents the earthworms Aporrectodea caliginosa. To evaluate the sublethal effects produced by dimethoate on worms, the activities of the acetylcholinesterase enzyme (AChE, the inhibition of which is the main mechanism of action of this type of compound) and glutathione S-transferase enzyme (GST, which is commonly activated as a pesticide detoxification mechanism) have been determined. The commercial product called DIMAFID40, whose active substance is the organophosphate pesticide dimethoate, was used. The selected concentrations were 0.06, 0.3 and 1.5 mg / kg of soil, each one tested in triplicate, using 10 worms per replicate.The AChE activity was significantly inhibited after exposure to the three assayed concentrations. With respect to GST activity, it was not increased but significantly inhibited after exposition to the highest concentration of pesticide. The non-appearance of an induction of GST activity may be due to the fact that the detoxification mechanism has not been started because the time of exposure to the pesticide has been too short. These results reflect the sensibility of AChE as a biomarker of the contamination in soils with organophosphate. (AU)


Assuntos
Animais , Dimetoato/efeitos adversos , Dimetoato/toxicidade , Inseticidas Organofosforados , Colinesterases , Glutationa Transferase , Biomarcadores Ambientais , Qualidade do Solo , Oligoquetos
5.
Comput Methods Programs Biomed ; 175: 129-137, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104702

RESUMO

BACKGROUND AND OBJECTIVE: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has been extensively used to analyse the complexity of structural and functional patterns of the human brain. In this study we investigate FD to assess whether it can discriminate between consciousness and different states of unconsciousness in healthy individuals. METHODS: We study 69 high-density electroencephalogram (hd-EEG) measurements after transcranial magnetic stimulation (TMS) in 18 healthy subjects progressing from wakefulness to non-rapid eye movement (NREM) sleep and sedation induced by different anaesthetic agents (xenon and propofol). We quantify the integration of thalamocortical networks by calculating the FD of a spatiotemporal voxelization obtained from the locations of all sources that are significantly activated by the perturbation (4DFD). Moreover, we study the temporal evolution of the evoked spatial distributions and compute a measure of the differentiation of the response by means of the Higuchi FD (HFD). Finally, a Fractal Dimension Index (FDI) of perturbational complexity is computed as the product of both quantities: integration FD (4DFD) and differentiation FD (HFD). RESULTS: We found that FDI is significantly lower in sleep and sedation when compared to wakefulness and provides an almost perfect intra-subject discrimination between conscious and unconscious states. CONCLUSIONS: These results support the combination of FD measures of cortical integration and cortical differentiation as a novel paradigm of tracking complex spatiotemporal dynamics in the brain that could provide further insights into the link between complexity and the brain's capacity to sustain consciousness.


Assuntos
Estado de Consciência , Eletroencefalografia , Estimulação Magnética Transcraniana , Inconsciência , Adolescente , Adulto , Anestesia , Encéfalo/diagnóstico por imagem , Feminino , Fractais , Voluntários Saudáveis , Humanos , Masculino , Propofol , Processamento de Sinais Assistido por Computador , Sono , Vigília , Xenônio , Adulto Jovem
6.
Sci Total Environ ; 679: 12-22, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31078771

RESUMO

Pesticides are one of the most frequently anthropogenic xenobiotics detected in water. Among these, the organophosphorus pesticides (OPs) are very widely used in agriculture due to their broad spectrum of activity and their low price, but they also have high potent effects as neurotoxic compounds in non-target organisms. The aim of this study was to evaluate biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), propionylcholinesterase (PChE) and carboxylesterase (CbE) in the representative Atlantic fish species Trachurus trachurus, Merluccius merluccius and Trisopterus luscus from "Rías Gallegas", a traditional Spanish fishing area. These esterase activities were evaluated in the brain, muscle and liver to determine the most adequate tissue to measure such enzymatic activities. The sensitivity of AChE and CbE activities from different tissues the widely used organophosphorus insecticide chlorpyrifos (CP), and its toxic metabolite (CP-oxon) was also tested. AChE activity was predominant in all tissues of the analysed species (particularly in brain constituting from 78.33%, 89.83% and 88.43% of total ChEs in Trachurus trachurus, Merluccius merluccius and Trisopterus luscus, respectively). Under in vitro exposure, esterases were shown to be highly sensitive to CP and especially to CP-oxon. Moreover, a similar effect observed on AChE and CbE activities could suggest that CbE activity might contribute efficiently against the toxic effects of CP, especially in muscle and the liver. The presence of BChE, PChE and upper CbE activities in muscle and the liver and their OP-sensibilities can be used to study their function in the pesticide biochemical detoxification pathways with a prominent role as a safeguarding mechanism against pesticide toxicity.


Assuntos
Clorpirifos/efeitos adversos , Esterases/metabolismo , Proteínas de Peixes/metabolismo , Gadiformes/metabolismo , Perciformes/metabolismo , Poluentes Químicos da Água/efeitos adversos , Animais , Monitoramento Ambiental , Inseticidas/efeitos adversos , Especificidade de Órgãos
7.
Rev. toxicol ; 36(2): 106-110, 2019. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-191871

RESUMO

La importancia de los estudios toxicológicos sobre suelos es evidente, y el desarrollo y uso de los ensayos estandarizados para llevarlos a cabo es un campo en constante crecimiento. En el presente trabajo se ha procedido a realizar el ensayo de toxicidad aguda con lombrices de tierra Eisenia foetida de acuerdo con el protocolo estandarizado de la OECD nº 207. La sustancia activa de elección ha sido el insecticida organofosforado dimetoato. A partir de la concentración recomendada por el fabricante del formulado comercial DIMAFID40, y siguiendo el protocolo arriba indicado, se ha realizado una exposición a 5 concentraciones diferentes del pesticida (0,001%; 0,01%; 0,1%; 1%; 10%), estableciéndose además un grupo control. Como primer resultado merece destacar que, a mayor dosis de ensayo del producto, mayor ha sido el porcentaje de mortalidad en los animales, observándose además mayores cambios fisio-patológicos en los animales expuestos. Dichos cambios no fueron evidentes en todos los grupos de animales, si bien fueron progresivos y cada vez más claros a medida que aumentaba la concentración de pesticida. La Concentración Letal Media (CL50) del ensayo coincidió con la concentración recomendada por el fabricante, estableciéndose en 0,1%. Por su parte, el Nivel sin efecto observable (NOEL), de gran relevancia ambiental, se alcanzó a una concentración diez veces inferior a la concentración recomendada por el fabricante


It is evident the relevance of toxicological studies on soils, and the development and use of standardized tests to carry them out is a field in constant growth. In the present work, the acute toxicity test with Eisenia foetida earthworms has been performed according to the standardized protocol of the OECD nº 207. The active substance of choice has been the organophosphate insecticide Dimethoate. Starting from the concentration recommended by the manufacturer of the commercial formulation DIMAFID40, an exposure to 5 different concentrations of the pesticide (0.001%; 0.01%; 0.1%; 1%; 10%) was performed, also establishing a control group. As a first result, it is worth mentioning that, the higher the test dose of the product, the higher the percentage of mortality in the animals. Furthermore, major physical-pathological changes were observed in exposed animals. These changes were not evident in all groups of animals, although they were progressive and clearly increasing as the concentration of pesticide raised. The lethal Media Concentration (LC50) of the trial coincided with the concentration recommended by the manufacturer, being set at 0.1%. Moreover, the level with no observed effect (NOEL), of great environmental relevance, was reached at a concentration ten times lower than the concentration recommended by the manufacturer


Assuntos
Animais , Inseticidas Organofosforados/análise , Dimetoato/análise , Dimetoato/toxicidade , Testes de Toxicidade/métodos , Oligoquetos/efeitos dos fármacos , Testes de Sensibilidade Parasitária , Fatores de Tempo , Dose Letal Mediana
8.
Ecotoxicol Environ Saf ; 164: 493-499, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30145489

RESUMO

Concentrations of 7 different polychlorinated biphenyl (PCB) congeners, and eleven organochlorine pesticides (OCPs) and metabolites, including DDTs (dichlorodiphenyltrichloroethane), HCHs (hexachlorocyclohexane isomers), Endosulfan, Endosulfan sulfate, Endrin, Dieldrin and HCB (hexachlorobenzene), were determined in adipose tissue of 57 yellow-legged gulls collected from NW and N Spain. Furthermore, the possible differences due to two endogenous factors, age and gender, were determined. All the analyzed PCBs were detected in over 66% of the samples, with levels of 291.9 (PCB 180), 34.5 (PCB 118), 0.7 (PCB 28), 432.6 (PCB 153), 225.5 (PCB 138), 1.3 (PCB 101) and 0.4 (PCB 52) µg/kg of adipose tissue. With respect to the OCPs and metabolites, only 4,4'-DDE and HCB were detected in more than 50% of the samples, with means of 360.6 and 2.5 µg/kg of adipose tissue, respectively. From all the considered contaminants, only 4,4'-DDE levels presented significant differences depending on the gender, with females showing higher values than males (p < 0.01). Significant differences (p < 0.001) were also found related to age for the levels of PCBs 180, 138, 101, 28 and 153, as well as 4,4'-DDE, with adult levels being higher than those in young birds. The results of the present study constitute a baseline to better assess the environmental impacts of PCB and OCP contamination at other coastal sites for future biomonitoring studies, with particular emphasis on gender- and age-related differences.


Assuntos
Tecido Adiposo/química , Charadriiformes/metabolismo , Poluentes Ambientais/análise , Hidrocarbonetos Clorados/análise , Bifenilos Policlorados/análise , Fatores Etários , Animais , DDT/análise , Monitoramento Ambiental , Feminino , Hexaclorobenzeno/análise , Hexaclorocicloexano/análise , Masculino , Praguicidas/análise , Fatores Sexuais , Espanha
9.
Clin. transl. oncol. (Print) ; 19(12): 1531-1536, dic. 2017. graf
Artigo em Inglês | IBECS | ID: ibc-168916

RESUMO

Purpose. Recently neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been reported to be inflammatory parameters that confer poorer outcome in metastatic castration-resistant prostate cancer (mCPRPC). However, these ratios have not been analyzed in patients treated with abiraterone acetate. We explored the relationship between different values of PLR and NLR and survival in mCPRCP treated with abiraterone and their possible relation with a prostate specific antigen (PSA) response. Methods. We retrospectively analyzed 101 patients with mCRPC treated with abiraterone from January of 2012 to November of 2015 in two different hospitals. A cut-off value of 5 for NLR and 150 for PLR were used to compare survival by Kaplan-Meier method. Moreover, an association between these cut-off values and the PSA response was analyzed by a χ2 test. Results. In the case of NLR, the median DFS were 12, 1 months for NLR <5 and 7 months for NLR ≥5, p = 0.061. The median OS were 23.9 months for NLR <5 and 16.3 months for NLR ≥5, p = 0.046. In the case of PLR, the median DFS were 11.8 months for PLR <150 and 10.6 months for PLR ≥150, p = 0.549. The median OS were 27.4 months for PLR <150 and 15.9 months for PLR ≥150, p = 0.005. It was not observed a correlation between the different cut-off values of PLR or NLR and a PSA response ≥25% (p = 0.31). Conclusions. It is shown a better prognostic relationship between PLR and NLR low values and OS that is statistically significant in mCPRC patients treated with abiraterone. Furthermore, it was not shown a relation between PLR and NLR values and PSA response (AU)


No disponible


Assuntos
Humanos , Masculino , Acetato de Abiraterona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Contagem de Plaquetas , Contagem de Linfócitos , Neutrófilos , Metástase Neoplásica/tratamento farmacológico , Antígeno Prostático Específico/análise
10.
Rev. toxicol ; 34(2): 124-129, jul.-dic. 2017. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-169822

RESUMO

En el presente estudio se investigó la sensibilidad de la actividad colinesterasa del sistema nervioso del conejo (Orictolagus cuniculus) al insecticida diazinón tanto in vivo como in vitro. En el ensayo in vivo, los animales fueron expuestos oralmente a dosis únicas de diazinón (25 o 125 mg/kg) y tras 10 días fueron sacrificados para obtener el cerebro, el cerebelo y la médula espinal. En ellos se determinó la actividad colinesterasa con el fin de conocer sus valores basales en conejo (grupo control) al igual que el potencial de inhibición in vivo originado por exposición a este pesticida (grupos expuestos). Los valores basales de actividad colinesterasa, usando la acetiltiocolina como sustrato, fueron 258.5 ± 38.0, 242.4 ± 32.0 y 235.1 ± 27.2 nmol/min.mg proteínas para el cerebro, el cerebelo y la médula espinal, respectivamente. En los grupos expuestos a diazinón no se observó inhibición de la actividad colinesterasa en comparación con la actividad del grupo control. En el ensayo in vitro se expusieron homogeneizados de los tres tejidos nerviosos de conejos control a distintas concentraciones de diazinón (0.025, 0.05, 0.1, 0.2 y 0.4 mg/l). La actividad colinesterasa permaneció constantemente deprimida en relación concentración y tiempo dependiente a lo largo del periodo experimental (30 minutos, 9, 24 y 48 horas) en todos los tejidos evaluados. La Concentración Inhibitoria Media (CI50) de la actividad AChE para el diazinón se estimó en 0.154, 0.138 y 0.159 mg/l para el cerebro, el cerebelo y la médula espinal, respectivamente. Se concluye la necesidad de establecimiento de una actividad basal o de referencia en cada laboratorio cuando se pretenda utilizar esta actividad con fines diagnósticos de exposición a plaguicidas anticolinesterásicos (AU)


In the current study, the in vivo and in vitro sensitivity of nervous system cholinesterase activity to pesticide diazinon in rabbits (Orictolagus cuniculus) was investigated. In the in vivo assay, animals were orally exposed to single doses of diazinon (25 or 125 mg/kg) and after 10 days were sacrificed to obtain the brain, cerebellum and spinal cord. The cholinesterase activity in these tissues was determined to know its basal values in rabbits (control group) as well as the potential in vivo inhibition caused by exposure to this pesticide (exposed groups). The basal values of cholinesterase activity were 258.5 ± 38.0, 242.4 ± 32.0 and 235.1 ± 27.2 nmol/min.mg protein to brain, cerebellum and spinal cord,respectively, using acetylthiocholine as substrate. No inhibition of cholinesterase activity in the exposed groups compared with the control group was observed at the end of the assay. In the in vitro assay, the supernatants of the homogenized of tissues were exposed to 0.025, 0.05, 0.1, 0.2 and 0.4 mg/l of diazinon. The cholinesterase activity remained steadily depressed in a concentration and time dependent relationship throughout the experimental period (30 minutes, 9, 24 and 48 hours) in all tissues assessed. The Mean Inhibitory Concentration (IC50) of cholinesterase activity to diazinon was estimated in 0.154, 0.138 and 0.159 mg/l to brain, cerebellum and spinal cord, respectively. To determine a basal activity in each laboratory is necessary to use this enzymatic activity for diagnostic purposes of exposure to anticholinesterase pesticides (AU)


Assuntos
Animais , Inseticidas Organofosforados/efeitos adversos , Sistema Nervoso , Colinesterases , Diazinon/farmacocinética , Coelhos , Compostos Organofosforados/toxicidade , Síndromes Neurotóxicas/fisiopatologia
11.
Clin Transl Oncol ; 19(12): 1531-1536, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28718070

RESUMO

PURPOSE: Recently neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have been reported to be inflammatory parameters that confer poorer outcome in metastatic castration-resistant prostate cancer (mCPRPC). However, these ratios have not been analyzed in patients treated with abiraterone acetate. We explored the relationship between different values of PLR and NLR and survival in mCPRCP treated with abiraterone and their possible relation with a prostate specific antigen (PSA) response. METHODS: We retrospectively analyzed 101 patients with mCRPC treated with abiraterone from January of 2012 to November of 2015 in two different hospitals. A cut-off value of 5 for NLR and 150 for PLR were used to compare survival by Kaplan-Meier method. Moreover, an association between these cut-off values and the PSA response was analyzed by a χ 2 test. RESULTS: In the case of NLR, the median DFS were 12, 1 months for NLR <5 and 7 months for NLR ≥5, p = 0.061. The median OS were 23.9 months for NLR <5 and 16.3 months for NLR ≥5, p = 0.046. In the case of PLR, the median DFS were 11.8 months for PLR <150 and 10.6 months for PLR ≥150, p = 0.549. The median OS were 27.4 months for PLR <150 and 15.9 months for PLR ≥150, p = 0.005. It was not observed a correlation between the different cut-off values of PLR or NLR and a PSA response ≥25% (p = 0.31). CONCLUSIONS: It is shown a better prognostic relationship between PLR and NLR low values and OS that is statistically significant in mCPRC patients treated with abiraterone. Furthermore, it was not shown a relation between PLR and NLR values and PSA response.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Plaquetas/patologia , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Taxa de Sobrevida
12.
Ecotoxicol Environ Saf ; 140: 24-29, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28231502

RESUMO

The aim of this study was to determine heavy metal reference levels for risk assessment studies. For this purpose, the levels of lead, cadmium, copper and zinc were determined in liver tissues of wild boars sampled in NW Spain. The mean values were 0.383, 0.326, 23.50 and 56.86mg/kg dried weight, respectively. In general, the levels detected were similar to or lower than the levels reported in literature. This study not only provides a useful baseline for biomonitoring the levels of the analyzed contaminants in wildlife in NW Spain, it also helps to understand the effects of gender on the levels of these elements. Similar to studies performed in other geographical regions, no significant gender-related differences could be detected. Although differences were not significant, the levels of zinc, cadmium and lead were modestly higher in males (55.78, 0.346 and 0.424mg/kg, respectively) compared to females (45.25, 0.305 and 0.341mg/kg). Our results indicate that, although gender did not significantly affect heavy metal uptake and toxicokinetics of contaminants in wild boars, these effects could vary between species, populations, organs, and elements. It is therefore essential to investigate gender-related differences for each species.


Assuntos
Monitoramento Ambiental/métodos , Fígado/metabolismo , Metais Pesados/farmacocinética , Caracteres Sexuais , Sus scrofa/metabolismo , Animais , Cádmio/farmacocinética , Cobre/farmacologia , Feminino , Fígado/efeitos dos fármacos , Masculino , Espanha , Suínos , Zinco/farmacologia
13.
Arch Environ Contam Toxicol ; 71(3): 313-21, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27475645

RESUMO

The aim of this study was to determine the levels of different inorganic elements (lead [Pb], mercury [Hg], and arsenic [As]) and persistent chlorinated pollutants (including polychlorinated biphenyls [PCBs] and organochlorine pesticides [OCPs]) in blood and plasma of White stork (Ciconia ciconia) nestlings from northwest (NW) Spain. The concentrations of PCBs were lower than the limit of detection in all samples. The OCPs γ-HCH, 4,4'-DDE, HCB, and endosulfan were detected most frequently in plasma from White stork nestlings. These OCPs were detected in 98, 54, 39, and 37 % of all samples, respectively. However, the concentrations of organic pollutants were lower than the risk thresholds for birds. The mean levels of the inorganic elements Pb, Hg, and As were found to be 36.92 ± 33.48, 16.48 ± 12.87, and 9.813 ± 13.84 µg/L, respectively. These levels were also lower than the risk thresholds for birds. This study not only provides a snapshot of the levels of both inorganic and organic contaminants in wild White storks in NW Spain, it also provides a useful baseline for biomonitoring levels of the measured contaminants in this area.


Assuntos
Aves/sangue , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Hidrocarbonetos Clorados/sangue , Metaloides/sangue , Metais/sangue , Animais , Espanha
14.
Knee Surg Sports Traumatol Arthrosc ; 24(6): 1826-35, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27120191

RESUMO

The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world's population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention. Growth factors, blood derivatives, such as platelet concentrates, and mesenchymal adult stem cells, either expanded or freshly isolated, are advocated amongst the most promising tool for the treatment of OA, especially in the early phases. Primarily targeted towards focal cartilage defects, these biological agents have indeed recently showed promising results to relieve pain and reduce inflammation in patients with more advanced OA as well, with the final aim to halt the progression of the disease and the need for joint replacement. However, despite of a number of satisfactory in vitro and pre-clinical studies, the evidences are still limited to support their clinical efficacy in OA setting.


Assuntos
Cartilagem Articular , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite do Joelho/terapia , Plasma Rico em Plaquetas , Regeneração , Tecido Adiposo/citologia , Progressão da Doença , Intervenção Médica Precoce , Humanos , Inflamação , Células-Tronco Mesenquimais , Osteoartrite/terapia , Dor
15.
Rev. chil. obstet. ginecol ; 80(3): 242-245, jun. 2015. ilus
Artigo em Espanhol | LILACS | ID: lil-752874

RESUMO

ANTECEDENTES: Frecuentemente, las pacientes con endometriosis presentan una elevación de marcadores tumorales Ca 125 y Ca 19.9. No obstante, no existe correlación clara con la expresión clínica ni con el grado de afectación. En algunos casos, es necesario un diagnóstico diferencial con patologías malignas. CASO CLÍNICO: Mujer de 29 años con clínica aislada de dismenorrea moderada y hallazgo de masas ováricas bilaterales con elevación intensa de marcadores tumorales: Ca-125: 7.716 U/mL y Ca-19.9: 995 U/mL. Se decide intervención quirúrgica laparoscópica evidenciándose endometriosis ovárica y extensión peritoneal masiva con afectación de peritoneo parietal abdominal, superficie uterina, fondo de Douglas, parametrios, vejiga, hemidiafragma derecho, hígado y serosa intestinal. Se realiza adhesiolisis cuidadosa, quistectomía y extirpación de múltiples implantes endometriósicos en cavidad abdominal. Se observó un descenso de los marcadores a las 48 horas: Ca-125 de 253 U/mL y Ca 19.9 de 4,9 U/mL, ambos negativos al mes de la cirugía. CONCLUSIÓN: Una elevación intensa de los marcadores tumorales precisa de diagnóstico diferencial en el contexto de la endometriosis. Existe una gran discrepancia entre los valores de los marcadores tumorales con la clínica y severidad de la endometriosis. Los hallazgos quirúrgicos son fundamentales, evidenciando una afectación masiva subdiagnosticada hasta la cirugía.


BACKGROUND: Frequently, patients with endometriosis present elevated tumor marker Ca 125 and Ca 19.9. However, there is no clear correlation with the clinical expression or the degree of involvement. In some cases, differential diagnosis is necessary with malignancies. CASE REPORT: A 29 year old woman with moderate dysmenorrhea and finding of bilateral ovarian masses with intense elevation of tumor markers, CA125: 7,716 U/mL and Ca-19.9: 995 U/mL. Laparoscopic surgery is decided evidenced massive ovarian endometriosis and peritoneal extension with involvement of abdominal peritoneum, uterine surface, Douglas, parametrium, bladder, right hemidiaphragm, liver and intestinal serosa. Careful liberation of adherences, ovarian cystectomy and removal of multiple endometriosic implants. A decrease of tumor markers was observed at 48 hours (Ca-125: 253 U/mL and Ca-19.9: 4.9 U/mL), and negative one month after surgery. CONCLUSION: An intense elevated tumor markers accurate differential diagnosis in the context of endometriosis. There is a large discrepancy between the values of tumor markers with clinical and severity of endometriosis.


Assuntos
Humanos , Feminino , Adulto , Antígeno Ca-125/análise , Endometriose/diagnóstico , Ovário , Peritônio , Biomarcadores Tumorais/análise , Laparoscopia , Antígeno CA-19-9/análise , Diagnóstico Diferencial , Dismenorreia , Endometriose/cirurgia
16.
Arch Environ Contam Toxicol ; 65(3): 567-74, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23619767

RESUMO

The effect of orally administered atrazine (25 or 100 mg/kg on days 0, 5, and 10 of the experiment) was studied in European quail (Coturnix coturnix coturnix) on four non-destructive biomarkers: fecal porphyrins, blood glutathione-S-transferase, glutathione reductase, reduced glutathione, and malondialdehyde (MDA). Uroporphyrin I (UPI) and coproporphyrins I and III (CPIII) were the main porphyrins detected in feces. The lowest dose of ATZ caused a significant (P < 0.05) increase in UPI and CPIII at day 5, and the highest dose of ATZ caused an induction of CPI and a significant (P < 0.05) decrease in MDA levels at day 30.


Assuntos
Atrazina/toxicidade , Coturnix/metabolismo , Exposição Ambiental , Herbicidas/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Fezes/química , Feminino , Fluorometria , Glutationa/sangue , Glutationa Redutase/sangue , Glutationa Transferase/sangue , Malondialdeído/sangue , Porfirinas/metabolismo , Espectrofotometria
18.
Farm. hosp ; 35(4): 189e1-189e4, jul.-ago. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-107330

RESUMO

Objetivo Revisión del tratamiento de la hidradenitis pupurativa y papel de etanercept en términos de eficacia y seguridad. Métodos Estudio descriptivo transversal retrospectivo. Se incluyeron pacientes diagnosticados de hidradenitis supurativa tratados con etanercept (indicación fuera de ficha técnica) hasta junio de 2009. Las variables estudiadas fueron: edad, sexo, tratamientos anteriores y posteriores a etanercept, respuesta, efectos adversos, duración y motivo de suspensión. Resultados Como primera línea de tratamiento se emplearon antibióticos, anticonceptivos, corticoides, isotretinoína o sulfonas orales. Ante la falta de respuesta mantenida se solicitó el uso de etanercept. Fue bien tolerado, pero únicamente permitió obtener una mejoría inicial, por lo que fue suspendido. Las siguientes opciones que se emplearon incluyeron corticoides, antibióticos, isotretinoína, anticonceptivos, inmunosupresores y antiandrógenos. Los pacientes tratados con adalimumab e infliximab como alternativa presentaron reactivación de las lesiones. Como última opción se plantea el tratamiento quirúrgico. Actualmente, la mayoría de los pacientes están en terapia de mantenimiento con tratamientos orales. Conclusiones El tratamiento de la hidradenitis supurativa se basa en antibióticos, corticoides o anticonceptivos con los que se obtiene un control transitorio de la enfermedad. El etanercept es bien tolerado, pero su eficacia se limita a una mejoría inicial. Se han obtenido resultados similares con infliximab y adalimumab. La cirugía permite obtener un control en la zona intervenida. Por tanto, el papel de los anti-TNF en el tratamiento de la hidradenitis supurativa es controvertido (AU)


Objective To review the treatment of hidradenitis suppurativa and the role of etanercept in terms of efficacy and safety. Methods Descriptive, cross-sectional and retrospective study. Patients diagnosed with hidradenitis suppurativa who were treated with etanercept (indication not on its Summary of Product Characteristics) until June 2009 were included in the study. The study variables were: age, sex, treatments before and after etanercept, response, adverse effects, duration and reason for stopping treatment. Results Antibiotics, contraceptives, corticosteroids, isotretinoin or oral sulfones were used as the first-line treatment. When patients no longer responded to these treatments, the use of etanercept was requested. It was well tolerated but it only led to an initial improvement. It was, therefore, suspended. The options employed included the following: corticosteroids, antibiotics, isotretinoin, contraceptives, immunosuppressive drugs and antiandrogens. Patients who were treated with adalimumab and infliximab as an alternative treatment found that their lesions flared up. Surgery was considered as a last option. At present, the majority of patients are undergoing maintenance therapy with oral treatments. Conclusions The treatment of hidradenitis suppurativa is based on antibiotics, corticosteroids or contraceptives. These are able to control the disease temporarily. Etanercept is well tolerated but it only results in an initial improvement. Similar results have been found with infliximab and adalimumab. The affected areas can be controlled with surgery. Therefore, the role of TNF inhibitors in the treatment of hidradenitis suppurativa is controversial (AU)


Assuntos
Humanos , Hidradenite Supurativa/tratamento farmacológico , Fatores de Necrose Tumoral/antagonistas & inibidores , Antibacterianos/uso terapêutico , Anticoncepcionais/uso terapêutico , Estudos Retrospectivos , Corticosteroides/uso terapêutico
19.
Sci Total Environ ; 408(21): 4976-83, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-20708216

RESUMO

In this study, the chronic effect of the insecticides carbofuran and deltamethrin on acetylcholinesterase (AChE) activity and malondialdehyde (MDA) and reduced glutathione (GSH) levels were examined in the brain of tench. Both pesticides were evaluated in two separate experiments, and animals were exposed in a continuous flow-system to three different concentrations of carbofuran (0, 10 and 100 microg/L) and deltamethrin (0, 0.0039 and 0.039 microg/L) for 60 days. After that period, animals were kept into pesticide-free water for other 30 days. In all cases, animals were sampled every 10 days all along the experience. AChE activity was significantly inhibited in fish exposed to 100 microg/L of carbofuran, during the first 30 days of exposition, returning to basal levels after this initial period. With respect to deltamethrin exposure, AChE activity was not significantly affected. When considering MDA levels, significant changes could only be detected during the recovery period for both pesticides, with a maximum of induction at 70 and 80 days, respectively associated to the highest dose of carbofuran and deltamethrin. Similarly, GSH levels varied all along the experience, with a maximum of significant increase at day 80 of exposition to the highest dose of both pesticides. This study shows that changes in AChE brain activity in tench can be used as a biomarker of early pesticide exposition in environmental monitoring programs, whereas MDA and GSH levels could be more associated to long-term expositions. The above results confirm and broaden former observations, suggesting that more investigations are needed before these biochemical parameters can be used as biomarkers.


Assuntos
Encéfalo/efeitos dos fármacos , Carbofurano/toxicidade , Cyprinidae/metabolismo , Inseticidas/toxicidade , Nitrilas/toxicidade , Piretrinas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Monitoramento Ambiental , Glutationa/metabolismo , Malondialdeído/metabolismo , Testes de Toxicidade Crônica , Poluentes Químicos da Água/toxicidade
20.
Philos Trans A Math Phys Eng Sci ; 368(1926): 4103-13, 2010 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-20679125

RESUMO

The muon ionization cooling experiment (MICE) will demonstrate a new technique for reducing the transverse emittance of a beam of muon particles, which are a species of lepton heavier than the electron species, essential for the realization of a future Neutrino Factory research facility. The first use of the Grid within MICE was to run thousands of Monte Carlo simulations to determine the alignment and statistical errors associated with measurements in MICE, which are made at two points in space on a similar sample of particles. The results of this study quantified the effect of correlations between emittance measurements. As a consequence, it has been determined that an order of magnitude less muons are required to achieve the required statistical accuracy than assuming uncorrelated measurements. This first application of the Grid within the MICE experimental domain has yielded results that could significantly impact upon the necessary running time of the experiment.

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