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1.
Phys Chem Chem Phys ; 19(7): 5246-5253, 2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-28149993

RESUMEN

The key challenges for perovskite solar cells include their poor stability and film homogeneity. Studying the degradation and homogeneity of perovskite layers within device structures can be challenging but critical to the understanding of stability and effect of processing in real life conditions. We show that Raman spectroscopy (RS) is a unique and powerful method (simple and fast) to probe the degradation of the perovskite film within the device structure and image perovskite formation. We demonstrate that RS can be used to directly probe chemical (PbI2) and physical (dihydrated phase) degradation of a perovskite film, and estimate the relative amount of the degradation species formed, mapping its distribution with ∼1 µm spatial resolution. This has been applied to mapping a large area perovskite module to characterise the efficacy of PbI2 to perovskite conversion. We also use RS to study the degradation species and kinetics under diverse accelerated degradation conditions (temperature and humidity) in situ. These capabilities are difficult to achieve with other methods, presenting RS as an important tool to gain understanding of the degradation and effect of processing on perovskite-based photovoltaic devices.

2.
Acta Physiol (Oxf) ; 213(2): 442-52, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25422088

RESUMEN

Neuropeptides represent an important category of endogenous contributors to the establishment and maintenance of immune deviation in the immune-privileged organs such as the CNS and in the control of acute inflammation in the peripheral immune organs. Vasoactive intestinal peptide (VIP) is a major immunoregulatory neuropeptide widely distributed in the central and peripheral nervous system. In addition to neurones, VIP is synthesized by immune cells which also express VIP receptors. Here, we review the current information on VIP production and VIP-receptor-mediated effects in the immune system, the role of endogenous and exogenous VIP in inflammatory and autoimmune disorders and the present and future VIP therapeutic approaches.


Asunto(s)
Enfermedades Autoinmunes/metabolismo , Inflamación/metabolismo , Neuropéptidos/metabolismo , Receptores de Péptido Intestinal Vasoactivo/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Animales , Humanos , Linfocitos T/metabolismo
3.
Environ Sci Technol ; 47(2): 1091-100, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-23181269

RESUMEN

Although two-dimensional electrophoresis (2D-GE) remains the basis for many ecotoxicoproteomic analyses, newer non-gel-based methods are beginning to be applied to overcome throughput and coverage limitations of 2D-GE. The overall objective of our research was to apply a comprehensive, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic approach to identify and quantify differentially expressed hepatic proteins from female fathead minnows exposed to fadrozole, a potent inhibitor of estrogen synthesis. Female fathead minnows were exposed to 0 (control), 0.04, and 1.0 µg of fadrozole/L of water for 4 days, and proteomic analysis was performed. Proteins were extracted and digested, and proteolytic peptides were separated via high-resolution one- or two-dimensional (1-D or 2-D) ultrapressure liquid chromatography (UPLC) and analyzed by tandem mass spectrometry. Mass spectra were searched against the National Center for Biotechnology Information (NCBI) ray-finned fish ( Actinopterygii ) database, resulting in identification of 782 unique proteins by single-dimension UPLC. When multidimensional LC analysis (2-D) was performed, an average increase of 1.9× in the number of identified proteins was observed. Differentially expressed proteins in fadrozole exposures were consistent with changes in liver function, including a decline in concentrations of vitellogenin as well as other proteins associated with endocrine function and cholesterol synthesis. Overall, these results demonstrate that a gel-free, label-free proteomic analysis method can successfully be utilized to determine differentially expressed proteins in small fish species after toxicant exposure.


Asunto(s)
Inhibidores de la Aromatasa/toxicidad , Cyprinidae/metabolismo , Fadrozol/toxicidad , Proteínas de Peces/metabolismo , Proteómica/métodos , Contaminantes Químicos del Agua/toxicidad , Animales , Cromatografía Liquida/métodos , Ecotoxicología/métodos , Femenino , Proteínas de Peces/aislamiento & purificación , Redes y Vías Metabólicas/efectos de los fármacos , Proteoma/aislamiento & purificación , Proteoma/metabolismo , Espectrometría de Masas en Tándem/métodos
4.
Indoor Air ; 22(6): 492-500, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22607315

RESUMEN

UNLABELLED: In 2005 through 2008, a small rural mountain valley community engaged in a woodstove changeout program to address concerns of poor ambient air quality. During this program, we assessed changes to indoor air quality before and after the introduction of a new, lower emission woodstove. We previously reported a >70% reduction in indoor PM(2.5) concentrations in homes following the installation of a new Environmental Protection Agency's-certified stove within the home. We report here on follow-up of the experiences in these and other homes over three winters of sample collection. In 21 homes, we compared pre-changeout PM(2.5) concentrations [mean (s.d.) = 45.0 (33.0) µg/m(3)] to multiple post-changeout measures of PM(2.5) concentrations using a DustTrak. The mean reduction (and 95% confidence interval) from pre-changeout to post-changeout was -18.5 µg/m(3) (-31.9, -5.2), adjusting for ambient PM(2.5) , ambient temperature, and other factors. Findings across homes and across years were highly variable, and a subset of homes did not experience a reduction in PM(2.5) following changeout. Reductions were also observed for organic carbon, elemental carbon, and levoglucosan, but increases were observed for dehydroabietic acid and abietic acid. Despite overall improvements in indoor air quality, the varied response across homes may be due to factors other than the introduction of a new woodstove. PRACTICAL IMPLICATIONS: Biomass combustion is a common source of ambient PM(2.5) in many cold-climate communities. The replacement of older model woodstoves with newer technology woodstoves is a potential intervention strategy to improve air quality in these communities. In addition to ambient air, woodstove changeouts should improve residential indoor air quality. We present results from a multi-winter study to evaluate the efficacy of woodstove changeouts on improving indoor air quality. Reductions in indoor PM(2.5) were evident, but this observation was not consistent across all homes. These findings suggest that other factors beyond the introduction of an improved wood burning device are relevant to improving indoor air quality in wood burning homes.


Asunto(s)
Contaminación del Aire Interior/análisis , Calefacción/instrumentación , Material Particulado/análisis , Carbono/análisis , Vivienda/estadística & datos numéricos , Compuestos Orgánicos/análisis , Temperatura , Madera
5.
Exp Neurol ; 217(1): 55-62, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19416674

RESUMEN

In rodents, spatial learning and memory tests require navigation, whereas in nonhuman primates these tests generally do not involve a navigational component, thus assessing nonhomologous neural systems. To allow closer parallels between rodent and primate studies, we developed a navigational spatial learning and memory task for nonhuman primates and assessed the performance of elderly (19-25 years) female rhesus monkeys (Macaca mulatta). The animals were allowed to navigate in a room containing a series of food ports. After they learned to retrieve food from the ports, a single port was repeatedly baited and the animals were tested until they learned the correct location. The location of the baited port was then changed (shift position). We also determined whether test performance was associated with circadian activity measured with accelerometers. Performance measures included trials to criterion, search strategies, and several indices of circadian activity. Animals learned the task as reflected in their search strategies. Correlations were found between the number of initial or shift trials and circadian activity parameters including day activity, dark:light activity ratio, sleep latency, and wake bouts. Thus, disruptions in circadian rhythms in nonhuman primates are associated with poorer performance on this novel test. These data support the usefulness of this spatial navigational test to assess spatial learning and memory in rhesus monkeys and the importance of circadian activity in performance.


Asunto(s)
Envejecimiento/fisiología , Aprendizaje por Asociación/fisiología , Ritmo Circadiano/fisiología , Macaca mulatta/fisiología , Memoria/fisiología , Conducta Espacial/fisiología , Animales , Discriminación en Psicología , Femenino , Estadística como Asunto
6.
Indoor Air ; 18(5): 408-15, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18665872

RESUMEN

UNLABELLED: During 2005-2007, a woodstove changeout program was conducted in a Rocky Mountain valley community in an effort to reduce ambient levels of PM(2.5). In addition to changes in ambient PM(2.5), an opportunity was provided to evaluate the changes in indoor air quality when old stoves were replaced with US Environmental Protection Agency (EPA)-certified woodstoves. PM(2.5) samples were measured in 16 homes prior to and following the changeout. For each sampling event, PM(2.5) mass was continuously measured throughout the 24-h sampling periods, and organic/elemental carbon (OC/EC) and associated chemical markers of woodsmoke were measured from quartz filters. Results showed that average PM(2.5) concentrations and maximum PM(2.5) concentrations were reduced by 71% and 76%, respectively (as measured by TSI DustTraks). Levoglucosan was reduced by 45% following the introduction of the new woodstove. However, the concentrations of resin acids, natural chemicals found in the bark of wood, were increased following the introduction of the new woodstove. There were no discernible trends in methoxphenol levels, likely due to the semi-volatile nature of the species that were measured. Although there is some uncertainty in this study regarding the amount of ambient PM infiltration to the indoor environment, these findings demonstrated a large impact on indoor air quality following this intervention. PRACTICAL IMPLICATIONS: Emissions from residential woodstoves are an important air quality issue (both indoors and ambient) in many regions throughout the US and the world. More specifically, woodstoves have been identified as a major source of PM(2.5) in valley locations throughout the Northern Rocky Mountains, where biomass combustion is the predominant source of home heating. In this study, we present results that demonstrate the dramatic reduction in PM(2.5) concentrations (as measured by TSI, Inc. DustTrak PM(2.5) air samplers) inside homes following the replacement of old, polluting woodstove with new EPA-certified woodstoves.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Culinaria/instrumentación , Incendios , Calefacción/instrumentación , Vivienda , Madera , Contaminantes Atmosféricos/química , Contaminación del Aire Interior/efectos adversos , Asma/inducido químicamente , Carbono/análisis , Carbono/química , Monitoreo del Ambiente , Filtración/instrumentación , Filtración/métodos , Humanos , Compuestos Orgánicos/análisis , Compuestos Orgánicos/química , Tamaño de la Partícula , Material Particulado/análisis , Material Particulado/química , Humo/análisis , Humo/prevención & control , Incertidumbre , Estados Unidos , United States Environmental Protection Agency , Salud Urbana
7.
Am J Physiol Renal Physiol ; 289(3): F521-30, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15870383

RESUMEN

Autosomal dominant polycystic kidney disease (ADPKD) types 1 and 2 arise as a consequence of mutations in the PKD1 or PKD2 genes, encoding polycystins-1 and -2. Because loss of function of either of the polycystins leads to a very similar phenotype and the two proteins are known to interact, polycystins-1 and -2 are probably active in the same pathway. The way in which loss of either polycystin leads to the development of ADPKD remains to be established, but disturbances of cell calcium regulation are likely to play an important role. Here, we demonstrate that polycystin-1, heterologously expressed in Madin-Darby canine kidney cells, had a pronounced effect on intracellular calcium homeostasis. ATP-induced calcium responses in transfection control cells exhibited a double peak and relatively gradual return to baseline. By contrast, cells expressing heterologous polycystin-1 showed a brief, uniphasic peak and an accelerated rate of decay. Heterologously expressed polycystin-1 accelerated endoplasmic reticulum (ER) calcium reuptake and inhibited capacitative calcium entry; we found no effect of the protein on mitochondrial calcium buffering or plasma membrane calcium extrusion. We therefore propose that polycystin-1 accelerated the decay of the cell calcium response to ATP by upregulation of ER calcium reuptake and consequent minimization of the stimulus for capacitative calcium entry. It is possible that cellular dedifferentiation, fluid secretion, and proliferation might therefore arise in ADPKD as a consequence of disturbances in cytoplasmic and ER calcium homeostasis and aberrant capacitative calcium entry.


Asunto(s)
Adenosina Trifosfato/farmacología , Calcio/farmacocinética , Retículo Endoplásmico/metabolismo , Riñón/citología , Proteínas/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Tampones (Química) , Línea Celular , Perros , Relación Dosis-Respuesta a Droga , Humanos , Ionomicina/farmacología , Ionóforos/farmacología , Ligandos , Mitocondrias/metabolismo , Proteínas/genética , Canales Catiónicos TRPP , Transfección
8.
Toxicol Appl Pharmacol ; 177(3): 188-99, 2001 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-11749118

RESUMEN

Hydrogen peroxide (H(2)O(2)) is present in the atmosphere at concentrations known to induce cell and tissue damage. However, inhaled H(2)O(2) vapor should not reach the lower lung due to its high water solubility. It has been suggested that hygroscopic components of particulate matter (PM) may transport H(2)O(2) into the lower lung and induce tissue injury and this was investigated. Ammonium sulfate [(NH(4))(2)SO(4)] was selected as a model for fine atmospheric PM. Treatment of female Sprague-Dawley rats with (NH(4))(2)SO(4) (429 or 215 microg/m(3); 0.3-0.4 microm mass median diameter) or H(2)O(2) (10, 20, or 100 ppb) alone or in combination for 2 h had no major effect on bronchoalveolar lavage fluid cell number or viability or on protein content or lactate dehydrogenase levels, either immediately or 24 h after exposure, relative to air-exposed rats. However, electron microscopy revealed increased numbers of neutrophils in pulmonary capillaries adhered to the vascular endothelium in rats treated with the combination of (NH(4))(2)SO(4) + H(2)O(2). Exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) also resulted in tumor necrosis factor-alpha (TNF-alpha) production by alveolar macrophages. This was observed immediately and 24 h after exposure. Immediately after inhalation of (NH(4))(2)SO(4) + H(2)O(2), a transient increase in production of superoxide anion by alveolar macrophages was observed. In contrast, nitric oxide production by cells from rats exposed to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2) alone was decreased, and this persisted for 24 h. Decreases in nitric oxide may be due to superoxide anion-driven formation of peroxynitrite. In this regard, nitrotyrosine, an in vivo marker of peroxynitrite, was detected in lung tissue after exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2). We also found that expression of the antioxidant enzyme heme oxygenase-1 by stimulated alveolar macrophages was increased following exposure of rats to (NH(4))(2)SO(4) + H(2)O(2). Taken together, these studies demonstrate that the biological effects of inhaled fine PM are augmented by H(2)O(2). Moreover, tissue injury induced by fine PM may be related to altered production of cytotoxic mediators by alveolar macrophages.


Asunto(s)
Aerosoles/toxicidad , Antioxidantes/metabolismo , Mediadores de Inflamación/metabolismo , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Enfermedades Respiratorias/metabolismo , Administración por Inhalación , Aerosoles/administración & dosificación , Sulfato de Amonio/administración & dosificación , Sulfato de Amonio/toxicidad , Animales , Líquido del Lavado Bronquioalveolar/citología , Ciclooxigenasa 2 , Femenino , Proteínas de Choque Térmico/metabolismo , Peróxido de Hidrógeno/administración & dosificación , Peróxido de Hidrógeno/toxicidad , Isoenzimas/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Macrófagos Alveolares/citología , Óxido Nítrico/metabolismo , Tamaño de la Partícula , Prostaglandina-Endoperóxido Sintasas/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Enfermedades Respiratorias/inducido químicamente , Enfermedades Respiratorias/patología , Organismos Libres de Patógenos Específicos , Factor de Necrosis Tumoral alfa/metabolismo
9.
Leuk Lymphoma ; 42(3): 491-8, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11699414

RESUMEN

We have previously shown that the Bcl-2 antisense oligonucleotide ODN 2009 can induce apoptosis in B-cell chronic lymphocytic leukaemia (B-CLL) cells. In this study we evaluated whether ODN 2009 could increase the sensitivity of B-CLL cells to Chlorambucil-induced cell death in vitro in order to establish whether the notion of antisense-mediated chemosensitisation could be applied to B-CLL. Bcl-2 antisense in combination with Chlorambucil resulted in a more marked reduction in Bcl-2 protein expression (p = 0.003), enhanced Bax expression (p < 0.0001) and increased apoptosis when compared to cells incubated with Chlorambucil alone (p = 0.03). This increased in vitro cytotoxicity demonstrates a proof of the concept that a combination of Bcl-2 antisense oligonucleotides with conventional chemotherapeutic drugs may elicit an enhanced therapeutic effect in B-CLL and should therefore be considered for further investigation in the form of a clinical trial.


Asunto(s)
Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Clorambucilo/toxicidad , Genes bcl-2 , Leucemia Linfocítica Crónica de Células B/patología , Oligodesoxirribonucleótidos Antisentido/toxicidad , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Biopsia , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Citometría de Flujo , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Células Tumorales Cultivadas , Proteína X Asociada a bcl-2
10.
J Assist Reprod Genet ; 18(9): 519-25, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11665668

RESUMEN

PURPOSE: To examine the effect of essential amino acids concentrations on mouse embryo development. METHODS: Mouse embryos were cultured in medium with different concentrations of essential amino acids and development to the blastocyst stage and viability assessed. Ammonium production resulting from medium breakdown and amino acid metabolism by embryos were also assessed. RESULTS: Reducing the essential amino acid concentration significantly increased blastocyst development and cell numbers. Lowering the essential amino acid concentration decreased ammonium production in the medium. CONCLUSIONS: Culture media for the development of preimplantation embryos should have a reduced essential amino acid concentration to facilitate embryo development.


Asunto(s)
Aminoácidos Esenciales/farmacología , Embrión de Mamíferos/citología , Embrión de Mamíferos/fisiología , Compuestos de Amonio Cuaternario/metabolismo , Animales , Células Cultivadas , Medios de Cultivo/química , Transferencia de Embrión , Embrión de Mamíferos/efectos de los fármacos , Desarrollo Embrionario y Fetal , Femenino , Muerte Fetal , Masculino , Ratones , Ratones Endogámicos , Embarazo
11.
Inhal Toxicol ; 12(6): 563-76, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10880144

RESUMEN

An aerosol generation and exposure system to evaluate the role of water-soluble gases in particulate matter (PM)-induced injury was designed, built, and validated by generating test atmospheres to study the role of hydrogen peroxide in PM-induced toxicity. In this system, particle number concentration, size distribution, hydrogen peroxide concentration, and water concentration can all be varied. An ammonium sulfate aerosol with mass median diameter 0.46 +/- 0.01 microm was used as a model atmospheric aerosol because ammonium sulfate is a major component of the fine aerosol, and the water uptake of ammonium sulfate aerosol is well characterized. The following four test atmospheres were generated: (1) ammonium sulfate aerosol, (2) an aerosol containing hydrogen peroxide and ammonium sulfate, (3) vapor-phase hydrogen peroxide, and (4) particle-free air. All test atmospheres were maintained at a relative humidity of 85%. Particle size distribution, number concentration, total hydrogen peroxide concentration, temperature, and relative humidity were measured continuously in the exposure chamber. The gas-particle partitioning of hydrogen peroxide was calculated using total hydrogen peroxide concentration, the Henry's law constant for hydrogen peroxide in water, and aerosol water content. We found that the aerosol generation system produced stable concentrations throughout the 2-hour exposures.


Asunto(s)
Contaminantes Atmosféricos/química , Cámaras de Exposición Atmosférica , Gases/química , Exposición por Inhalación , Aerosoles , Contaminantes Atmosféricos/toxicidad , Sulfato de Amonio , Animales , Diseño de Equipo , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/toxicidad , Tamaño de la Partícula , Solubilidad , Agua
12.
Environ Health Perspect ; 108(5): 387-92, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10811563

RESUMEN

Levels of the polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, appear to be rising rapidly in human tissues, as evidenced by studies of human breast milk. The case of the PBDEs illustrates the value of breast-milk monitoring programs in identifying important emerging pollutants, and highlights why such monitoring programs are needed in the United States. A review of the use, occurrence, and toxicity of PBDEs indicates many parallels between some PBDEs, PCBs, and other polyhalogenated persistent organic pollutants, and suggests that the PBDEs may be a significant environmental challenge in the future.


Asunto(s)
Leche Humana/química , Éteres Fenílicos/análisis , Bifenilos Polibrominados/análisis , Animales , Glándulas Endocrinas/efectos de los fármacos , Salud Ambiental , Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Contaminantes Ambientales/toxicidad , Femenino , Retardadores de Llama/análisis , Retardadores de Llama/toxicidad , Humanos , Sistema Nervioso/efectos de los fármacos , Sistema Nervioso/embriología , Sistema Nervioso/crecimiento & desarrollo , Éteres Fenílicos/toxicidad , Bifenilos Polibrominados/toxicidad , Receptores de Hidrocarburo de Aril/efectos de los fármacos , Estados Unidos
13.
J Biomed Mater Res ; 50(3): 365-74, 2000 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-10737878

RESUMEN

Using a rodent air pouch, the inflammatory responses to biomaterials with distinct physical properties and chemical compositions were compared. The polymers examined were expanded poly(tetrafluoroethylene) (ePTFE), silicone, low-density polyethylene (LDPE), poly(L-lactic acid) (PLLA), poly(desaminotyrosyl-tyrosine ethyl carbonate) [poly(DTE carbonate)], and poly(desaminotyrosyl-tyrosine benzyl carbonate) [poly(DTBzl carbonate)]. We found that implantation of disks (4.5-4.8 mm) of these materials into rodent air pouches for 2 days had no effect on the number or type of cells recovered relative to sham controls. With each of the materials, macrophages were the predominant cell type identified (60-75%), followed by granulocytes (20-25%) and lymphocytes (10%). Implantation of poly(DTE carbonate), ePTFE, LDPE, or poly(DTBzl carbonate) into the pouches for 2 days caused an increase in release of superoxide anion by the pouch cells. Cells from pouches containing poly(DTE carbonate) also released more hydrogen peroxide and were more phagocytic. In contrast, PLLA and silicone had no effect on the functional activity of cells recovered from the pouches. Prolonging the implantation time of poly(DTE carbonate) or PLLA to 7 days did not alter the number or type of cells isolated from the pouches. However, cells from pouches containing poly(DTE carbonate) for 7 days continued to produce increased quantities of superoxide anion relative to sham control pouch cells. These results suggest that the air pouch model is a highly sensitive method and therefore useful for evaluating the functional responses of inflammatory cells to biomaterials.


Asunto(s)
Materiales Biocompatibles , Inflamación/inducido químicamente , Polímeros , Animales , Materiales Biocompatibles/efectos adversos , Femenino , Microscopía Electrónica de Rastreo , Polímeros/efectos adversos , Ratas , Ratas Sprague-Dawley
14.
Environ Health Perspect ; 107(6): 447-57, 1999 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10515712

RESUMEN

High levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; up to 208 pg/g fat) were measured in samples of breast milk collected in 1997 from 64 donors [41 first-time mothers (primiparae)] living on state farms in southern Kazakhstan. TCDD was the major contributor (70%) to the toxic equivalents, matching the congener patterns found in breast milk and serum samples collected in 1994 and 1996 from donors in nearby villages. The highest TCDD levels were found in state farms adjacent to a reservoir (zone A), which receives agricultural runoff from cotton fields. TCDD levels in zone A were significantly higher than levels in a region more distant (zone B; > 10 miles) from the reservoir (zone A: mean 53 pg/g, n = 17; zone B: mean 21 pg/g, n = 24; p = 0.0017). Levels of TCDD in breast milk and animal-derived foodstuffs were 10 times U.S. levels. Body burden and dietary data suggest that exposures to TCDD are chronic, environmental, and long term and may be related to the use of chemicals in cotton agriculture. The data suggest that the most likely source is the use of cotton defoliants contaminated with TCDD, and the most likely pathway for human exposure is via the consumption of contaminated foodstuffs.


Asunto(s)
Agricultura , Exposición a Riesgos Ambientales/análisis , Leche Humana/química , Dibenzodioxinas Policloradas/análisis , Adulto , Envejecimiento/metabolismo , Benzofuranos/análisis , Dieta , Femenino , Análisis de los Alimentos , Humanos , Kazajstán , Población Rural , Encuestas y Cuestionarios
16.
Anal Chem ; 71(1): 212-20, 1999 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-9921129

RESUMEN

Limits of quantitation (LOQs) for a quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) method were evaluated through replicate analysis of unfortified peanut oil, shortening, lamb fat, and butter for all 2,3,7,8-chlorine-substituted polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs). Ten congeners were measurable in butter (0.27-2.5 pg/g) and nine congeners were measurable in lamb fat (0.09-2.6 pg/g) with good precision. LOQs for high-fat foods were estimated by triplicate analysis of peanut oil fortified at two levels. Accurate and reproducible results were achieved at 0.5 pg/g for most PCDD/Fs (1.0 pg/g for heptachlorodibenzo-p-dioxin and heptachlorodibenzofuran and 2.0 pg/g for octachlorodibenzofuran) and at 0.2 pg/g for 2,3,7,8-tetrachlorodibenzofuran (TCDF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). QISTMS distinguished between catfish and chicken eggs with elevated TCDD levels from background samples collected from the most regions of the continental United States. QISTMS determined the extent of TCDD contamination in butter, lamb fat, and cottonseed oil collected from rural villages in Kazakhstan. Replicate analysis of catfish and chicken eggs by the QISTMS method produced comparable results to high-resolution mass spectrometry (HRMS). Lower limits of detection will be needed if QISTMS is to fully complement HRMS in the measurement of TCDD levels in food.


Asunto(s)
Grasas de la Dieta/análisis , Dioxinas/análisis , Análisis de los Alimentos/métodos , Animales , Mantequilla/análisis , Indicadores y Reactivos , Espectrometría de Masas , Carne/análisis , Aceite de Cacahuete , Aceites de Plantas/análisis , Dibenzodioxinas Policloradas/análisis , Control de Calidad , Ovinos
17.
Environ Health Perspect ; 106(12): 797-806, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9831540

RESUMEN

To assess levels of chlorinated contaminants in breast milk, we measured organochlorine pesticides, polychlorinated biphenyls, polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) in breast milk samples collected in 1994 according to the World Health Organization protocol from 92 donors that were representative of regional populations in southern Kazakstan. High levels (10-120 pg/g fat) of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic of the PCDD/PCDF congeners, were found in breast milk samples from an agricultural region. TCDD was the major contributor (75%) to the international toxicity equivalents of these samples. The same distinctive PCDD/PCDF congener pattern was found in 15 breast milk samples and 4 serum samples collected in 1996 in a follow-up study, and has now been confirmed by three analytical laboratories.


Asunto(s)
Benzofuranos/análisis , Exposición a Riesgos Ambientales , Leche Humana/química , Dibenzodioxinas Policloradas/análogos & derivados , Contaminantes del Suelo/análisis , Adolescente , Adulto , Agricultura , Benzofuranos/toxicidad , Femenino , Humanos , Kazajstán , Dibenzodioxinas Policloradas/análisis , Dibenzodioxinas Policloradas/toxicidad , Embarazo , Valores de Referencia , Contaminantes del Suelo/toxicidad
18.
J Biomed Mater Res ; 41(3): 443-54, 1998 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-9659614

RESUMEN

Previous studies demonstrated that poly(DTE carbonate) and poly (DTE adipate), two tyrosine-derived polymers, have suitable properties for use in biomedical applications. This study reports the evaluation of the in vivo tissue response to these polymers in comparison to poly(L-lactic acid) (PLLA). Typically, the biocompatibility of a material is determined through histological evaluations as a function of implantation time in a suitable animal model. However, due to changes that can occur in the tissue response at different stages of the degradation process, a fixed set of time points is not ideal for comparative evaluations of materials having different rates of degradation. Therefore the tissue response elicited by poly(DTE carbonate), poly(DTE adipate), and PLLA was evaluated as a function of molecular weight. This allowed the tissue response to be compared at corresponding stages of degradation. Poly(DTE adipate) consistently elicited the mildest tissue response, as judged by the width and lack of cellularity of the fibrous capsule formed around the implant. The tissue response to poly(DTE carbonate) was mild throughout the 570 day study. However, the response to PLLA fluctuated as a function of the degree of degradation, exhibiting an increase in the intensity of inflammation as the implant began to lose mass. At the completion of the study, tissue ingrowth into the degrading and disintegrating poly(DTE adipate) implant was evident while no comparative ingrowth of tissue was seen for PLLA. The similarity of the in vivo and in vitro degradation rates of each polymer confirmed the absence of enzymatic involvement in the degradation process. A comparison of molecular weight retention, water uptake, and mass loss in vivo with two commonly used in vitro systems [phosphate-buffered saline (PBS) and simulated body fluid (SBF)] demonstrated that for the two tyrosine-derived polymers the in vivo results were equally well simulated in vitro with PBS and SBF. However, for PLLA the in vivo results were better simulated in vitro using PBS.


Asunto(s)
Materiales Biocompatibles/metabolismo , Implantes Experimentales , Ácido Láctico/metabolismo , Nylons/metabolismo , Poliésteres/metabolismo , Polímeros/metabolismo , Animales , Materiales Biocompatibles/química , Estudios de Evaluación como Asunto , Femenino , Hidrólisis , Ácido Láctico/química , Espectroscopía de Resonancia Magnética , Nylons/química , Poliésteres/química , Polímeros/química , Ratas , Ratas Sprague-Dawley
19.
Chemosphere ; 37(3): 431-42, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9661274

RESUMEN

We have characterized the spectrum of PCB contaminants in human milk samples from 95 women in Kazakhstan using GC/MS congener specific analysis. In these samples, 12 PCBs comprised 83% of total PCB concentration, and were similar to the major PCBs reported in other published human milk studies. By summing concentration levels of 80 PCB congeners in the Kazakhstan samples, a mean total PCB concentration of 368 ng/g fat was obtained. This is lower than levels reported in human milk samples from Western Europe. Six indicator PCBs were summed in Kazakh milk samples; their aggregate value was similar to literature values published for human milk from the former Soviet Union. Using WHO's recent TEF scheme, the mean sum of PCDD/F, coplanar PCB, mono-ortho PCB, and di-ortho PCB TEQ is 42 pg TEQ/g fat.


Asunto(s)
Leche Humana/química , Bifenilos Policlorados/análisis , Contaminantes del Suelo/análisis , Benzofuranos/análisis , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lactante , Recién Nacido , Kazajstán , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/análisis , Organización Mundial de la Salud
20.
Neurosci Lett ; 237(2-3): 69-72, 1997 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-9453217

RESUMEN

The activity of single neurons in the striatum of freely moving rats was recorded in response to systemic administration of dopamine agonists selective for either the D1 or D2 family of receptors. At a dose that induced behavioral activation, SKF-38393 (5.0 mg/kg s.c.), a D1 agonist, had no consistent effect on striatal activity, whereas quinpirole (1.0-5.0 mg/kg s.c.), a D2 agonist, inhibited the great majority of striatal neurons. In addition, quinpirole (1.0 mg/kg s.c.) excited neurons of the globus pallidus, which receives an inhibitory projection from the striatum. These results are consistent with models of the basal ganglia in which dopamine, via D2 receptors, inhibits striatopallidal activity, resulting in a disinhibition of neurons in globus pallidus.


Asunto(s)
Agonistas de Dopamina/farmacología , Globo Pálido/fisiología , Neostriado/fisiología , Neuronas/efectos de los fármacos , Quinpirol/farmacología , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Ganglios Basales/efectos de los fármacos , Electrofisiología , Globo Pálido/citología , Globo Pálido/efectos de los fármacos , Masculino , Neostriado/citología , Neostriado/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Dopamina D1/efectos de los fármacos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/efectos de los fármacos , Receptores de Dopamina D2/metabolismo , Estimulación Química
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