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1.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1559906

RESUMO

Introducción: Las fracturas del antebrazo comprometen la diáfisis del radio y el cúbito. Su relación anatómica desempeña un papel importante porque el antebrazo se vincula con los movimientos de la mano para garantizar la función de la extremidad y de los tejidos blandos. Objetivo: Evaluar los resultados del tratamiento de la fractura diafisiarias de antebrazo con placa de compresión dinámica. Métodos: Se realizó un estudio prospectivo, longitudinal y descriptivo en 28 pacientes con fractura diafisaria de antebrazo, intervenidos quirúrgicamente con placa de compresión dinámica en el Hospital Ortopédico Docente "Fructuoso Rodríguez". Los resultados fueron evaluados según la escala funcional de Grace-Eversmann. Resultados: La edad media fue de 38 años, con una proporción entre sexos de 2,1:1. Predominaron las fracturas del tercio medio del radio y del cúbito. Se afectó más el lado izquierdo, pero en el 75 % de los casos hubo un excelente resultado. No se registraron fallas con la técnica quirúrgica aplicada. Conclusiones: La osteosíntesis con placa de compresión dinámica en las fracturas diafisarias de antebrazo es una alternativa adecuada para garantizar tasas de consolidación elevadas y resultados funcionales excelentes.


Introduction: Fractures of the forearm compromise the diaphysis of the radius and ulna. Their anatomical relationship plays an important role because the forearm is linked to hand movements to ensure limb and soft tissue function. Objective: To evaluate the results of treating diaphyseal forearm fracture with dynamic compression plate. Methods: A prospective, longitudinal and descriptive study was carried out in 28 patients with diaphyseal fracture of the forearm. They underwent surgery with a dynamic compression plate at Fructuoso Rodríguez Teaching Orthopedic Hospital. The results were evaluated according to Grace-Eversmann functional scale. Results: The mean age was 38 years, with a gender ratio of 2.1:1. Fractures of the middle third of the radius and ulna predominated. The left side was affected more, but 75% of the cases had excellent result. No failures were recorded with the applied surgical technique. Conclusions: Osteosynthesis with dynamic compression plating in diaphyseal fractures of the forearm is a suitable alternative to guarantee high consolidation rates and excellent functional results.

2.
Chem Res Toxicol ; 36(1): 43-52, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36598842

RESUMO

Little filtered cigars are tobacco products with many cigarette-like characteristics. However, despite cigars falling under the U.S. Food and Drug Administration regulatory authority, characterizing flavors, which are still allowed in little filtered cigars, and filter design may influence how people use the products and the resulting exposure to harmful and potentially harmful constituents. We estimated nicotine mouth level intake (MLI) from analyses of little cigar filter butt solanesol levels, brand characteristics, carbon monoxide boost, and puff volume in 48 dual cigarette/cigar users during two repeat bouts of ad lib smoking of three little filtered cigar brands. Mean nicotine MLI for the three brands was significantly different with Swisher Sweets (0.1% ventilation) Cherry at 1.20 mg nicotine, Cheyenne Menthol (1.5%) at 0.63 mg, and Santa Fe unflavored (49%) at 0.94 mg. The association between nicotine MLI and puff volume was the same between Cheyenne Menthol and Santa Fe unflavored. However, these were different from Swisher Sweets Cherry. At least five main factors─flavor, ventilation, filter design, nicotine delivery related to tar, and user puff volume─may directly or indirectly impact MLI and its association with other measures. We found that users of little filtered cigars that have different filter ventilation and flavor draw dissimilar amounts of nicotine from the product, which may be accompanied by differences in exposure to other harmful smoke constituents.


Assuntos
Nicotina , Produtos do Tabaco , Adulto , Humanos , Nicotina/análise , Mentol , Produtos do Tabaco/análise , Fumar , Nicotiana , Boca/química
3.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1559895

RESUMO

Introducción: La fractura del extremo distal del húmero constituye un verdadero reto para los traumatólogos. Se han diseñado numerosos métodos de tratamiento quirúrgico para restaurar anatómicamente la superficie articular y lograr una estabilidad que permita la movilidad y la pronta incorporación del paciente a sus actividades diarias. Objetivo: Evaluar los resultados del tratamiento quirúrgico de la fractura del húmero distal con placas perpendiculares Métodos: Se realizó un estudio prospectivo, longitudinal, descriptivo en 18 pacientes con fractura del húmero distal, intervenidos quirúrgicamente con el sistema de placas perpendiculares en el Hospital Ortopédico Docente "Fructuoso Rodríguez" en el período 2017-2020. Los resultados se evaluaron según la escala de la clínica Mayo para la función del codo. Resultados: Se estudiaron 18 casos con un promedio de edad de 49 años. El tipo de fractura más frecuente fue la simple articular. Al año la flexoextensión media fue de 1120/160 y la pronosupinación de 810/800. La complicación más común fue la rigidez articular. El 50 % de los resultados fueron excelentes. Conclusiones: El tratamiento de la fractura de húmero distal con placas perpendiculares ofreció buenos resultados clínicos y funcionales por lo que constituye una opción válida en el Hospital Ortopédico Docente "Fructuoso Rodríguez".


Introduction: The fracture of the distal end of the humerus is a real challenge for traumatologists. Numerous surgical treatment methods have been designed to anatomically restore the joint surface and achieve stability that allows mobility and prompt return of the patient to daily activities. Objective: To evaluate the results of the surgical treatment of the distal humerus fracture with perpendicular plates. Methods: A prospective, longitudinal, descriptive study was carried out in 18 patients with fractures of the distal humerus, who underwent surgery with the perpendicular plate system. The results were evaluated according to Mayo Clinic scale for elbow function. Results: Eighteen cases with an average age of 49 years were studied. The most frequent type of fracture was simple joint. At one year, mean flexoextension was 1120/160 and pronosupination 810/800. The most common complication was joint stiffness. 50% of the results were excellent. Conclusions: The treatment of the distal humerus fracture with perpendicular plates offered good clinical and functional results, in consequence it constitutes a valid option at Fructuoso Rodríguez Orthopedic Teaching Hospital.

4.
J Chromatogr A ; 1565: 124-129, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29945789

RESUMO

Nitrobenzene, a potentially harmful compound found in tobacco smoke, has been largely excluded from prior analysis due to difficulties with quantification. Quantifying harmful compounds in cigarette smoke is useful to compare products, to examine the impact of design parameters on delivery, and to help estimate exposures. A sensitive high-throughput method has been developed for quantifying nitrobenzene in machine-generated mainstream cigarette smoke using isotope dilution gas chromatography-tandem mass spectrometry (ID-GC-MS/MS). This method has sufficient sensitivity to measure vapor phase nitrobenzene concentrations in the low nanogram range, with a 418 pg/cig method limit of detection. Precision estimates from two quality control cigarette products resulted in percent relative standard deviations of 11.5% and 14.9%; product variability estimates from 13 cigarette products resulted in percent relative standard deviations ranging from 2.8% to 16.9%. Nitrobenzene in the machine-generated, mainstream smoke from 15 cigarette products are reported and range from 18 to 38 ng/cig under the Health Canada Intense smoking regimen.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Nicotiana/química , Nitrobenzenos/análise , Poluição por Fumaça de Tabaco/análise , Calibragem , Canadá , Íons , Limite de Detecção , Material Particulado/análise , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Produtos do Tabaco/análise
5.
Tob Regul Sci ; 3(1): 81-94, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28220149

RESUMO

OBJECTIVE: Our objective was to characterize mainstream smoke constituent deliveries from SPECTRUM variable nicotine research cigarettes under 2 machine smoking regimens. SPECTRUM cigarettes are manufactured by the 22nd Century company for the National Institute on Drug Abuse, National Institutes of Health to contain varying (including reduced) levels of nicotine. METHODS: Mainstream smoke constituent deliveries of "tar," nicotine, carbon monoxide, tobacco-specific nitrosamines (N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)), benzo[a]pyrene, aromatic amines, and carbonyls were analyzed in 23 varieties of SPECTRUM cigarettes using ISO 17025 accredited methods. RESULTS: Data are presented as means and standard deviations of 5 replicates for all analytes. CONCLUSIONS: Under the ISO smoking regimen, mean levels of many smoke emissions for SPECTRUM varieties were comparable to the 3R4F research cigarette. Calculated SPECTRUM elasticity ranged from 1.6 to 4.0. Accordingly, under intense machine smoking conditions differences in emissions of SPECTRUM cigarettes were apparent. In addition, NNN increased with smoke nicotine while the same rate of change was not seen for NNK. It is important to monitor levels of chemicals of public health concern and regulatory interest as technologies emerge to reduce levels of nicotine or other targeted chemicals in tobacco products.

6.
Chem Res Toxicol ; 29(6): 1051-63, 2016 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-27222918

RESUMO

The aim of this study is to explore how differences in cigarette physical design parameters influence tar, nicotine, and carbon monoxide (TNCO) yields in mainstream smoke (MSS) using the International Organization of Standardization (ISO) smoking regimen. Standardized smoking methods were used to evaluate 50 U.S. domestic brand cigarettes and a reference cigarette representing a range of TNCO yields in MSS collected from linear smoking machines using a nonintense smoking regimen. Multivariate statistical methods were used to form clusters of cigarettes based on their ISO TNCO yields and then to explore the relationship between the ISO generated TNCO yields and the nine cigarette physical design parameters between and within each cluster simultaneously. The ISO generated TNCO yields in MSS are 1.1-17.0 mg tar/cigarette, 0.1-2.2 mg nicotine/cigarette, and 1.6-17.3 mg CO/cigarette. Cluster analysis divided the 51 cigarettes into five discrete clusters based on their ISO TNCO yields. No one physical parameter dominated across all clusters. Predicting ISO machine generated TNCO yields based on these nine physical design parameters is complex due to the correlation among and between the nine physical design parameters and TNCO yields. From these analyses, it is estimated that approximately 20% of the variability in the ISO generated TNCO yields comes from other parameters (e.g., filter material, filter type, inclusion of expanded or reconstituted tobacco, and tobacco blend composition, along with differences in tobacco leaf origin and stalk positions and added ingredients). A future article will examine the influence of these physical design parameters on TNCO yields under a Canadian Intense (CI) smoking regimen. Together, these papers will provide a more robust picture of the design features that contribute to TNCO exposure across the range of real world smoking patterns.


Assuntos
Modelos Estatísticos , Fumaça/análise , Produtos do Tabaco/análise , Monóxido de Carbono/análise , Monóxido de Carbono/normas , Cooperação Internacional , Análise Multivariada , Nicotina/análise , Nicotina/normas , Padrões de Referência , Alcatrões/análise , Alcatrões/normas , Produtos do Tabaco/normas
7.
Transl Res ; 176: 38-68, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27220087

RESUMO

Ulcerative colitis and Crohn's disease are the 2 major phenotypes of inflammatory bowel disease (IBD), which are influenced by a complex interplay of immunological and genetic elements, though the precise etiology still remains unknown. With IBD developing into a globally prevailing disease, there is a need to explore new targets and a thorough understanding of the pathophysiological differences between the healthy and diseased gut could unearth new therapeutic opportunities. In this review, we provide an overview of the major aspects of IBD pathogenesis and thereafter present a comprehensive analysis of the gut pathophysiology leading to a discussion on some of the most promising targets and biologic therapies currently being explored. These include various gut proteins (CXCL-10, GATA-3, NKG2D, CD98, microRNAs), immune cells recruited to the gut (mast cells, eosinophils, toll-like receptors 2, 4), dysregulated proinflammatory cytokines (interleukin-6, -13, -18, -21), and commensal microbiota (probiotics and fecal microbiota transplantation). We also evaluate some of the emerging nonconventional therapies being explored in IBD treatment focusing on the latest developments in stem cell research, oral targeting of the gut-associated lymphoid tissue, novel anti-inflammatory signaling pathway targeting, adenosine deaminase inhibition, and the beneficial effects of antioxidant and nutraceutical therapies. In addition, we highlight the growth of biologics and their targets in IBD by providing information on the preclinical and clinical development of over 60 biopharmaceuticals representing the state of the art in ulcerative colitis and Crohn's disease drug development.


Assuntos
Trato Gastrointestinal/fisiopatologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Terapia de Alvo Molecular , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/patologia , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Microbiota/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
8.
Int J Pharm ; 502(1-2): 181-7, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26892815

RESUMO

Monoclonal antibodies (mAbs) are highly effective therapeutic agents, administered exclusively by the parenteral route owing to their previously-documented instability in the gastrointestinal (GI) tract when delivered orally. To investigate the extent of the validity of this assumption, the stability of the tumor necrosis factor alpha (TNF-α) neutralizing IgG1 mAbs, infliximab and adalimumab, was studied in human GI conditions. In gastric fluid, infliximab and adalimumab degraded rapidly, with complete degradation occurring within 1 min. In small intestinal fluid, the molecules were shown to be more stable, but nonetheless degraded within a short time frame of 30 min. Investigations into the mechanisms responsible for infliximab and adalimumab instability in the small intestine revealed that the proteolytic enzyme elastase, and to a lesser extent the enzymes trypsin and chymotrypsin, was responsible for their degradation. By contrast, in the human colon, 75% and 50% of the dose of infliximab and adalimumab, respectively, were intact after 60 min, with conversion of mAbs into F(ab')2 Fab and Fc fragments detected in colonic conditions. These data indicate that therapeutic IgG1 antibodies are more stable in the colon than in the upper GI tract, therefore highlighting the potential for oral delivery of anti-TNF-α mAbs targeted to the colon.


Assuntos
Adalimumab/química , Infliximab/química , Antirreumáticos/química , Quimotripsina/química , Colo/metabolismo , Fezes/química , Suco Gástrico/química , Humanos , Imunoglobulina G/imunologia , Secreções Intestinais/química , Elastase Pancreática/química , Pancreatina/química , Tripsina/química , Fator de Necrose Tumoral alfa/imunologia
9.
Tob Regul Sci ; 2(2): 94-105, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26779559

RESUMO

OBJECTIVE: To provide researchers an extensive characterization of the SPECTRUM variable nicotine research cigarettes. METHODS: Data on cigarette physical properties, nicotine content, harmful and potentially harmful constituents in the tobacco filler was compiled. RESULTS: Data on physical properties, concentrations of menthol, nicotine and minor alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, ammonia, and toxic metals in the filler tobacco for all available varieties of Spectrum research cigarettes are provided. The similarity in the chemistry and physical properties of SPECTRUM cigarettes to commercial cigarettes renders them acceptable for use in behavioral studies. Baseline information on harmful and potentially harmful constituents in research tobacco products, particularly constituent levels such as minor alkaloids that fall outside typical ranges reported for commercial, provide researchers with the opportunity to monitor smoking behavior and to identify biomarkers that will inform efforts to understand the role of nicotine in creating and sustaining addiction. CONCLUSIONS: Well characterized research cigarettes suitable for human consumption are an important tool in clinical studies for investigating the physiological impacts of cigarettes delivering various levels of nicotine, the impact of reduced nicotine cigarettes on nicotine addiction, and the relationship between nicotine dose and smoking behavior.

10.
Pediátr. Panamá ; 44(1): 33-36, Abril-Mayo 2015.
Artigo em Espanhol | LILACS | ID: biblio-848706

RESUMO

Introducción: El síndrome de Marshall o PFAPA, por sus siglas en inglés (Periodic fever, aphtas, pharyngitis and cervical adenopathies), es una patología que se caracteriza principalmente por cuadros de ebres periódicas asociadas a faringitis y estomatitis. Los pacientes suelen recibir múltiples cursos de antibióticos antes de ser diagnosticados. Se desconoce su causa exacta, el diagnóstico es clínico y se con rma con la mejoría del cuadro luego de la administración de prednisona oral. Caso clínico: Se presenta el caso de una paciente de 4 años de edad quien inició con episodios febriles recurrentes desde los 9 meses de edad y luego de múltiples ciclos de antibióticos se sospecha el Síndrome de Marshall el cual mejoró luego del abordaje terapeútico dirigido. Discusión: El síndrome de Marshall o PFAPA es una entidad que debe ser considerada durante la atención primaria en aquellos pacientes que acuden frecuentemente por cuadros de ebre, faringitis y estomatitis aftosas. La sospecha de este diagnóstico mejora la calidad de vida del paciente y sus familiares considerando la ansiedad que produce a los padres llevar a su niño con frecuencia al cuarto de urgencias.


Introduction: Marshall syndrome or PFAPA (Periodic fever, aphtas, pharyngitis and cervical adenopathies), is a condition that is mainly characterized by periodic fevers associated with pharyngitis and stomatitis. Patients usually receive multiple courses of antibiotics before being diagnosed. The exact cause is unknown, the diagnosis is clinical and con rmed with the improvement of the condition after administration of oral prednisone. Case report: We report a case of a 4 year old girls who started with recurrent febrile episodes from 9 months and after multiple courses of antibiotics, Marshall Syndrome was suspected and patient improved after targeted therapy. Discussion: Marshall Syndrome or PFAPA is a condition that must be considered during primary care attention of those patients who frequently consult by cyclic episodes of fever, pharyngitis and aphthous stomatitis. The suspicion of this diagnosis improves the quality of life of patients and their families considering the anxiety of parents who needs to take their child to the emergency

11.
Artigo em Inglês | MEDLINE | ID: mdl-23648311

RESUMO

Organophosphate and pyrethroid insecticides and phenoxyacetic acid herbicides represent important classes of pesticides applied in commercial and residential settings. Interest in assessing the extent of human exposure to these pesticides exists because of their widespread use and their potential adverse health effects. An analytical method for measuring 12 biomarkers of several of these pesticides in urine has been developed. The target analytes were extracted from one milliliter of urine by a semi-automated solid phase extraction technique, separated from each other and from other urinary biomolecules by reversed-phase high performance liquid chromatography, and detected using tandem mass spectrometry with isotope dilution quantitation. This method can be used to measure all the target analytes in one injection with similar repeatability and detection limits of previous methods which required more than one injection. Each step of the procedure was optimized to produce a robust, reproducible, accurate, precise and efficient method. The required selectivity and sensitivity for trace-level analysis (e.g., limits of detection below 0.5ng/mL) was achieved using a narrow diameter analytical column, higher than unit mass resolution for certain analytes, and stable isotope labeled internal standards. The method was applied to the analysis of 55 samples collected from adult anonymous donors with no known exposure to the target pesticides. This efficient and cost-effective method is adequate to handle the large number of samples required for national biomonitoring surveys.


Assuntos
Herbicidas/urina , Espectrometria de Massas/métodos , Praguicidas/urina , Piretrinas/urina , Extração em Fase Sólida/métodos , Humanos , Organofosfatos/urina , Reprodutibilidade dos Testes
12.
Int Rev Cell Mol Biol ; 301: 215-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23317820

RESUMO

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of re-establishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies.


Assuntos
Retículo Endoplasmático/metabolismo , Resposta a Proteínas não Dobradas , Animais , Doença , Retículo Endoplasmático/ultraestrutura , Estresse do Retículo Endoplasmático , Humanos , Proteólise
13.
Int J Environ Res Public Health ; 8(8): 3063-98, 2011 08.
Artigo em Inglês | MEDLINE | ID: mdl-21909292

RESUMO

Organophosphorus (OP) insecticides were among the first pesticides that EPA reevaluated as part of the Food Quality Protection Act of 1996. Our goal was to assess exposure to OP insecticides in the U.S. general population over a six-year period. We analyzed 7,456 urine samples collected as part of three two-year cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. We measured six dialkylphosphate metabolites of OP pesticides to assess OP pesticide exposure. In NHANES 2003-2004, dimethylthiophosphate was detected most frequently with median and 95th percentile concentrations of 2.03 and 35.3 µg/L, respectively. Adolescents were two to three times more likely to have diethylphosphate concentrations above the 95th percentile estimate of 15.5 µg/L than adults and senior adults. Conversely, for dimethyldithiophosphate, senior adults were 3.8 times and 1.8 times more likely to be above the 95th percentile than adults and adolescents, respectively, while adults were 2.1 times more likely to be above the 95th percentile than the adolescents. Our data indicate that the most vulnerable segments of our population-children and older adults-have higher exposures to OP pesticides than other population segments. However, according to DAP urinary metabolite data, exposures to OP pesticides have declined during the last six years at both the median and 95th percentile levels.


Assuntos
Exposição Ambiental/análise , Inseticidas/metabolismo , Inseticidas/urina , Inquéritos Nutricionais , Compostos Organofosforados/metabolismo , Compostos Organofosforados/urina , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Análise de Regressão , Fatores de Tempo , Estados Unidos , Adulto Jovem
14.
J Cell Sci ; 124(Pt 13): 2143-52, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21628424

RESUMO

Increasing evidence indicates that endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR), but that beyond a certain degree of ER damage, this response triggers apoptotic pathways. The general mechanisms of the UPR and its apoptotic pathways are well characterized. However, the metabolic events that occur during the adaptive phase of ER stress, before the cell death response, remain unknown. Here, we show that, during the onset of ER stress, the reticular and mitochondrial networks are redistributed towards the perinuclear area and their points of connection are increased in a microtubule-dependent fashion. A localized increase in mitochondrial transmembrane potential is observed only in redistributed mitochondria, whereas mitochondria that remain in other subcellular zones display no significant changes. Spatial re-organization of these organelles correlates with an increase in ATP levels, oxygen consumption, reductive power and increased mitochondrial Ca²âº uptake. Accordingly, uncoupling of the organelles or blocking Ca²âº transfer impaired the metabolic response, rendering cells more vulnerable to ER stress. Overall, these data indicate that ER stress induces an early increase in mitochondrial metabolism that depends crucially upon organelle coupling and Ca²âº transfer, which, by enhancing cellular bioenergetics, establishes the metabolic basis for the adaptation to this response.


Assuntos
Retículo Endoplasmático/metabolismo , Metabolismo Energético , Mitocôndrias/metabolismo , Estresse Fisiológico , Antibacterianos/farmacologia , Apoptose/fisiologia , Cálcio/metabolismo , Respiração Celular , Inibidores Enzimáticos/farmacologia , Células HeLa , Agonistas dos Receptores Histamínicos/farmacologia , Humanos , Potencial da Membrana Mitocondrial , Consumo de Oxigênio/efeitos dos fármacos , Fosfatos de Fosfatidilinositol/metabolismo , Transdução de Sinais/fisiologia
15.
Environ Health Perspect ; 118(6): 856-63, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20129873

RESUMO

BACKGROUND: We measured 34 metabolites of current-use pesticides and other precursor compounds in urine samples collected twice during pregnancy from 538 women living in the Salinas Valley of California, a highly agricultural area (1999-2001). Precursors of these metabolites included fungicides, carbamate, organochlorine, organophosphorus (OP), and pyrethroid insecticides, and triazine and chloroacetanilide herbicides. We also measured ethylenethiourea, a metabolite of the ethylene-bisdithiocarbamate fungicides. Repeat measurements of the compounds presented here have not been reported in pregnant women previously. To understand the impact of the women's regional environment on these findings, we compared metabolite concentrations from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) cohort with U.S. national reference data for 342 pregnant women sampled by the National Health and Nutrition Examination Survey (1999-2002). RESULTS: The eight metabolites detected in > 50% of samples [2,4-dichlorophenol (2,4-DCP); 2,5-dichlorophenol (2,5-DCP); 1- and 2-naphthol; ortho-phenylphenol (ORTH); para-nitrophenol (PNP); 2,4,6-trichlorophenol (2,4,6-TCP); and 3,4,6-trichloro-2-pyridinol (TCPy)] may be related to home or agricultural pesticide use in the Salinas Valley, household products, and other sources of chlorinated phenols. More than 78% of women in this study had detectable levels of at least one of the OP pesticide-specific metabolites that we measured, and > 30% had two or more. The 95th percentile values of six of the most commonly detected (> 50%) compounds were significantly higher among the CHAMACOS women after controlling for age, race, socioeconomic status, and smoking [(2,4-DCP; 2,5-DCP; ORTH; PNP; 2,4,6-TCP; and TCPy); quantile regression p < 0.05]. CONCLUSIONS: Findings suggest that the CHAMACOS cohort has an additional burden of precursor pesticide exposure compared with the national sample, possibly from living and/or working in an agricultural area.


Assuntos
Exposição Ambiental/análise , Monitoramento Ambiental/estatística & dados numéricos , Resíduos de Praguicidas/urina , Análise de Variância , California , Cromatografia Gasosa , Estudos de Coortes , Creatinina/urina , Feminino , Humanos , Entrevistas como Assunto , Inquéritos Nutricionais , Gravidez
16.
Biochim Biophys Acta ; 1802(6): 509-18, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20176105

RESUMO

Aggresomes are dynamic structures formed when the ubiquitin-proteasome system is overwhelmed with aggregation-prone proteins. In this process, small protein aggregates are actively transported towards the microtubule-organizing center. A functional role for autophagy in the clearance of aggresomes has also been proposed. In the present work we investigated the molecular mechanisms involved on aggresome formation in cultured rat cardiac myocytes exposed to glucose deprivation. Confocal microscopy showed that small aggregates of polyubiquitinated proteins were formed in cells exposed to glucose deprivation for 6 h. However, at longer times (18 h), aggregates formed large perinuclear inclusions (aggresomes) which colocalized with gamma-tubulin (a microtubule-organizing center marker) and Hsp70. The microtubule disrupting agent vinblastine prevented the formation of these inclusions. Both small aggregates and aggresomes colocalized with autophagy markers such as GFP-LC3 and Rab24. Glucose deprivation stimulates reactive oxygen species (ROS) production and decreases intracellular glutathione levels. ROS inhibition by N-acetylcysteine or by the adenoviral overexpression of catalase or superoxide dismutase disrupted aggresome formation and autophagy induced by glucose deprivation. In conclusion, glucose deprivation induces oxidative stress which is associated with aggresome formation and activation of autophagy in cultured cardiac myocytes.


Assuntos
Autofagia/fisiologia , Glucose/deficiência , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Multimerização Proteica , Acetilcisteína/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Autofagia/efeitos dos fármacos , Catalase/metabolismo , Células Cultivadas , Glucose/metabolismo , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Corpos de Inclusão/metabolismo , Microscopia Eletrônica de Transmissão , Centro Organizador dos Microtúbulos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Transporte Proteico , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Tubulina (Proteína)/metabolismo , Ubiquitina/metabolismo
18.
J Expo Sci Environ Epidemiol ; 17(6): 559-66, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17534384

RESUMO

Acetochlor is a preemergent chloroacetanilide herbicide used to control annual grasses and small-seeded broadleaf weeds. It is the second most abundantly applied herbicide on corn crops in the United States; however, human metabolites associated with known exposure to acetochlor have not been positively identified and confirmed. We positively identified acetochlor mercapturate (ACM) as a metabolite of acetochlor in urine samples collected during a 24-h period from custom (commercial) applicators who had applied acetochlor on either the day of or the day before urine collection. Concentrations in applicator urine samples ranged from 0.5 to 449 microg/l (0.3-121 microg/g creatinine). We found that ACM accounted for as much as 42% of the total acetochlor-derived metabolites; however, as the exposure level decreased (based on total acetochlor metabolite level), ACM became a less abundant metabolite of acetochlor (<17%). Unmetabolized acetochlor was also measured in the urine samples analyzed. At high exposures (classified as >100 microg/l), acetochlor accounted for about 0.8% of the total excreted acetochlor metabolites (approximately 2% of the ACM concentrations). At lower exposures (classified as ACM<10 microg/l), ACM and acetochlor concentrations were similar. Additionally, we tentatively identified another acetochlor metabolite that appeared to be important at low levels of exposure.


Assuntos
Acetilcisteína/análogos & derivados , Poluentes Ocupacionais do Ar/urina , Herbicidas/urina , Exposição Ocupacional/análise , Toluidinas/urina , Acetilcisteína/urina , Agricultura , Cromatografia Líquida de Alta Pressão , Humanos , Masculino , Espectrometria de Massas
19.
Environ Health Perspect ; 114(9): 1419-23, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16966099

RESUMO

We conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. We substituted most of the children's conventional diets with organic food items for 5 consecutive days and collected two daily spot urine samples, first morning and before bedtime voids, throughout the 15-day study period. We analyzed urine samples for five common pyrethroid metabolites. We found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. We conclude that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.


Assuntos
Dieta , Poluentes Ambientais/toxicidade , Praguicidas/toxicidade , Piretrinas/toxicidade , População Suburbana , População Urbana , Fatores Etários , Criança , Pré-Escolar , Monitoramento Ambiental , Poluentes Ambientais/urina , Humanos , Lactente , Estudos Longitudinais , Praguicidas/urina , Piretrinas/urina , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
20.
Environ Health Perspect ; 114(2): 260-3, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16451864

RESUMO

We used a novel study design to measure dietary organophosphorus pesticide exposure in a group of 23 elementary school-age children through urinary biomonitoring. We substituted most of children's conventional diets with organic food items for 5 consecutive days and collected two spot daily urine samples, first-morning and before-bedtime voids, throughout the 15-day study period. We found that the median urinary concentrations of the specific metabolites for malathion and chlorpyrifos decreased to the nondetect levels immediately after the introduction of organic diets and remained nondetectable until the conventional diets were reintroduced. The median concentrations for other organophosphorus pesticide metabolites were also lower in the organic diet consumption days; however, the detection of those metabolites was not frequent enough to show any statistical significance. In conclusion, we were able to demonstrate that an organic diet provides a dramatic and immediate protective effect against exposures to organophosphorus pesticides that are commonly used in agricultural production. We also concluded that these children were most likely exposed to these organophosphorus pesticides exclusively through their diet. To our knowledge, this is the first study to employ a longitudinal design with a dietary intervention to assess children's exposure to pesticides. It provides new and persuasive evidence of the effectiveness of this intervention.


Assuntos
Dieta , Exposição Ambiental/prevenção & controle , Alimentos Orgânicos , Compostos Organofosforados/urina , Praguicidas/urina , Agricultura , Criança , Pré-Escolar , Humanos , Estudos Longitudinais , Compostos Organofosforados/metabolismo , Praguicidas/metabolismo
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