Diseño y validación de una rúbrica para evaluar las habilidades socioemocionales en estudiantes de enfermería / Design and validation of an instrument to assess the social and emotional skills of nursing students / Desenho e validação de uma rubrica para avaliar habilidades socioemocionais em estudantes de enfermagem

RESUMEN Introducción Las habilidades socioemocionales (HSE) hacen referencia a las actuaciones integrales representadas mediante la conducta para un adecuado manejo de emociones, realización personal y desarrollo social. Existen diversos instrumentos de evaluación para medir las HSE en universitarios, pero son inexistentes los dirigidos a estudiantes de enfermería. Objetivo Diseñar y determinar la validez de contenido de un instrumento para evaluar HSE en estudiantes de enfermería. Metodología Se realizó un estudio instrumental que incluyó las fases de revisión de instrumentos para evaluar las HSE; construcción del instrumento; revisión y mejora del instrumento por expertos; validación de contenido mediante el juicio de 16 expertos empleando un índice de relevancia (V de Aiken); pilotaje del instrumento con 50 estudiantes para el análisis de confiabilidad (Alpha de Cronbach) y comprensión del instrumento. Resultados El instrumento integró 12 indicadores (tolerancia, trabajo colaborativo, adaptación al entorno, comunicación eficaz, empatía, toma de decisiones, creatividad, relaciones interpersonales, asertividad, autoeficacia, resiliencia, y manejo del estrés). El juicio de expertos reveló la validez de contenido (V de Aiken > 0.90). Se obtuvo un valor aceptable de confiabilidad (α= 0.786) y una adecuada opinión sobre la comprensión del instrumento en el pilotaje. Discusión y Conclusión La evaluación de HSE en estudiantes de enfermería es fundamental tanto para mejorar y mantener su salud mental como para favorecer el desarrollo profesional, personal y social. La rúbrica es un instrumento confiable, primero en su tipo y con validez de contenido. Para que obtenga una calidad óptima se requiere continuar con el análisis de sus propiedades psicométricas.

ABSTRACT Introduction Social-emotional Skills (SES) refer to integral behaviors representing ade- quate management of emotions while achieving personal and social development. There are diverse instruments to assess SES on university students in general, but not on nursing students in particular. Objective To design an instrument to assess SES among nursing students and test its content validity. Methodology An instrumental study was carried out that included the revision phases of instruments to evaluate the SES: construction of the instrument; review and improvement of the instrument by experts; content validation by 16 experts using Aiken's V relevance index; and pilot test of the instrument on 50 students and assess its reliability (Cronbach´s Alpha) and ease of comprehension. Results The instrument integrated 12 indicators (tolerance, collaborative work, adaptation to the environment, efficacious communication, empathy, decision making, creativity, interpersonal relationships, assertiveness, self-efficacy, resilience, and stress management). Expert judgment revealed a content validity of Aiken's V > 0.90. An acceptable value of reliability (α= 0.786) and favorable opinion was obtained regarding the ease of comprehension of the instrument. Discussion and Conclusion The assessment of SES on nursing students is fundamental to improve and preserve their mental health, and foster their professional, personal, and social development. This is a reliable, first-of-its-kind, and content-validated instrument. Nevertheless, the analysis of its psychometric properties should be continued to keep improving its quality.

RESUMO Introdução As habilidades socioemocionais (HSE) referem-se a ações integrais representadas por meio do comportamento para o manejo adequado de emoções, realização pessoal e desenvolvimento social. Existem diversos instrumentos de avaliação para mensurar a HSE em estudantes universitários, mas os voltados para estudantes de enfermagem são inexistentes. Objetivo Desenhar e determinar a validade de conteúdo de um instrumento para avaliar HSE em estudantes de enfermagem. Metodologia Foi realizado um estudo instrumental que incluiu as fases de revisão dos instrumentos de avaliação da HSE; construção de instrumentos; revisão e aperfeiçoamento do instrumento pelos especialistas; validação de conteúdo por meio dos pareceres de 16 especialistas utilizando um índice de relevância (V de Aiken); pilotagem do instrumento com 50 alunos para análise da confiabilidade (Alpha de Cronbach) e compreensão do instrumento. Resultados O instrumento integrou 12 indicadores (tolerância, trabalho colaborativo, adaptação ao entorno, comunicação efetiva, empatia, tomada de decisão, criatividade, relacionamento interpessoal, assertividade, autoeficácia, resiliência e gerenciamento de estresse). O parecer de especialistas revelou validade de conteúdo (V de Aiken > 0.90). Obteve-se um valor aceitável de confiabilidade (α= 0.786) e uma opinião adequada sobre o entendimento do instrumento na pilotagem. Discussão e Conclusão A avaliação da HSE em estudantes de enfermagem é essencial tanto para melhorar e manter sua saúde mental quanto para promover o desenvolvimento profissional, pessoal e social. A rubrica é um instrumento confiável, primeiro do gênero e com validade de conteúdo. Para obter a qualidade ideal, é necessário continuar com a análise de suas propriedades psicométricas.

[Clinical and radiographic evaluation of a new percutaneous technique for moderate to severe hallux valgus deformity]. / Evaluación clínica y radiográfica de una nueva técnica percutánea para la corrección de la deformidad en hallux valgus moderada a severa.

Hallux valgus is considered the most common musculoskeletal deformity, with a prevalence of 88%. There are more than 130 surgical techniques for its treatment; currently, percutaneous ones are popular; however, they do not take into account the metatarsal-phalangeal correction angle. The aim of this study is to propose a modified technique for the correction of the percutaneous metatarsal-phalangeal and inter-metatarsal angles and to evaluate its clinical and radiological results. MATERIAL AND METHODS: An experimental, prospective and longitudinal study in 10 patients with moderate to severe hallux valgus according to the classification of Coughlin and Mann were collected; the results were evaluated with the AOFAS scale at 15, 30, 60 and 90 days. The McBride technique and the technique of percutaneous anchor with the proposed amendment were performed. RESULTS: The AOFAS scale was applied as described, finding a progressive increase of the rating; the average correction of the inter-metatarsal angle was 8.8 degrees and of the metatarsal-phalangeal, 9.12. DISCUSSION: The modified technique of percutaneous anchor showed clear clinical and radiographic improvements in the short term. Our modified technique is proposed for future projects, including a large sample with long-term follow-up.

El hallux valgus es considerado la deformidad del aparato locomotor más frecuente, con una prevalencia de 88%. Existen más de 130 técnicas quirúrgicas para su tratamiento; actualmente se encuentra de moda el uso de técnicas de anclaje percutáneas; sin embargo, no toman en cuenta la corrección del ángulo metatarsofalángico. El objetivo del siguiente estudio es mostrar la técnica modificada de anclaje percutáneo con corrección del ángulo metatarsofalángico e intermetatarsiano, así como la evaluación clínica y radiológica. Material y métodos: Se realizó un estudio experimental, prospectivo y longitudinal en una muestra de 10 pacientes con el diagnóstico de hallux valgus moderado a severo según la clasificación Coughlin y Mann; se evaluaron los resultados con la escala de AOFAS a los 15, 30, 60 y 90 días. Se realizaron las técnicas de McBride y de anclaje percutáneo con la modificación propuesta. Resultados: La escala AOFAS mostró un aumento progresivo de la puntación; la corrección media del ángulo intermetatarsiano fue de 8.8 grados y del metatarsofalángico, 9.12. Discusión: La técnica modificada de anclaje percutáneo mostró evidente mejoría clínica y radiográfica en el seguimiento de los pacientes, lo que comprueba que es una técnica aceptable a mediano plazo. Nuestra técnica modificada se desarrollará como una línea de investigación a futuro con un mayor número de pacientes y seguimiento a largo plazo.

[Sonographic evaluation of Achilles tendon healing in tenotomies for congenital clubfoot and Ponsetis treatment. A 12-week follow-up]. / Evaluación ultrasonográfica del tendón de Aquiles en niños con pie equino varo aducto congénito posterior a tenotomía de Aquiles con el método de Ponseti. Seguimiento a 12 semanas.

OBJECTIVE: The aim of this study was to determine the healing time of Achilles tendon in pediatric patients treated with Achilles tenotomy with the Ponseti method in Shriners Childrens Hospital of Mexico, AC. MATERIAL AND METHODS: Experimental, analytical, prospective, longitudinal study of patients with a diagnosis of idiopathic congenital clubfoot treated with the Ponseti method with serial static and dynamic evaluation by ultrasound in real time with a Siemens Diagnostic Ultrasound System Sonoline 650, linear transducer 10.5 MHz of Achilles tendon before tenotomy and at three, six, nine and 12 weeks after the surgical treatment. RESULTS: A sample of 23 patients, 16 male and seven female, 16 with unilateral and seven with bilateral pathology was obtained, for a total of 39 feet, 18 right and 21 left, with a mean age of 8.3 ± 2.3 months. Before tenotomy, the width was 2.7 ± 0.42 mm; in week three, the average was 3 ± 0.39 mm; at six weeks, 2.92 ± 0.36 mm; ultrasound at nine weeks reported an average of 0.38 ± 2.84 mm, and 2.82 ± 0.39 mm at twelve weeks. They were compared using Students t presurgical width and at twelve weeks, without finding difference p 0.03. CONCLUSIONS: Although there is integrity at three weeks after Achilles tenotomy, complete repair is achieved at 12 weeks.

OBJETIVO: Determinar el tiempo de curación del tendón de Aquiles en pacientes pediátricos tratados mediante tenotomía de Aquiles con método Ponseti en el Hospital Shriners para Niños de México, AC. MATERIAL Y MÉTODOS: Estudio experimental, analítico, prospectivo, longitudinal de pacientes con diagnóstico de pie equino varo aducto congénito idiopático en tratamiento con método Ponseti con evaluación estática y dinámica mediante ecógrafo en tiempo real Siemens Diagnostic Ultrasound System Sonoline 650 con transductor lineal de 10.5 mHz seriada del tendón de Aquiles previa a la tenotomía y a las tres, seis, nueve y 12 semanas tras el tratamiento quirúrgico. RESULTADOS: Se obtuvo una muestra de 23 pacientes, 16 masculinos y siete femeninos, 16 con patología bilateral y siete unilateral, para un total de 39 pies, 18 derechos y 21 izquierdos, con una media de edad de 8.3 ± 2.3 meses. Previamente a la tenotomía, la anchura en corte longitudinal ultrasonográfico media fue de 2.7 ± 0.42 mm; en la semana tres, la media fue 3 ± 0.39 mm; a las seis semanas, 2.92 ± 0.36 mm; el ultrasonido de las nueve semanas reportó media de 2.84 ± 0.38 mm y a las 12 semanas, 2.82 ± 0.39 mm. Se compararon mediante t de Student el ancho prequirúrgico y a las 12 semanas, sin encontrarse diferencia p 0.03. CONCLUSIONES: La valoración ecográfica muestra integridad a las tres semanas posteriores a la tenotomía de Aquiles. Sin embargo, la reparación completa se logra a las 12 semanas.

[Functional results of open wedge osteotomies in lower limb angular deformities in teenagers]. / Resultados funcionales en pacientes adolescentes con corrección de deformidades angulares de los miembros inferiores tratados con osteotomía en cuña abierta.

OBJECTIVE: The aim of this study was to evaluate the functional and radiographic results of adolescent patients with angular deformities of the pelvic limbs treated with an open wedge osteotomy system. MATERIAL AND METHODS: Observational, prospective, analytical and cross-sectional study of patients with angular deformity of the pelvic limbs treated with an open wedge osteotomy. We made a radiographic evaluation of the femorotibial angle, MAD angle, lower limb discrepancy, and pre- and postoperative degrees of the rotational center of deformity (CORA), as well as a telephone survey of the postoperative functional evaluation IKDC 2000. RESULTS: It was a sample of 28 patients, 21 female and seven male, with a mean age of 15.3 years. Their diagnoses: idiopathic genu valgo, 10 cases; Blount disease, four; benign tumors (enchondromatosis and osteochondromatosis), three; hypophosphatemic rickets; three, among others, such as sequelae of septic arthritis of the knee, femoral hypoplasia, and fracture sequels. It was a total of 29 osteotomies, 17 of the tibia and 12 of the femur; 17 osteotomies presented deviation to lateral of the mechanical axis, and 11, medial deviation, with a mean femorotibial angle of 17 and 7.35 (p 0.03), respectively. The mean initial discrepancy had an improvement of 0.5 cm. Postoperative IKDC in the subjective evaluation had an average of 95.3 points. CONCLUSIONS: The fixation of osteotomies with open wedge plates is an option with good clinical and radiographic results.

OBJETIVO: Evaluar los resultados funcionales y radiográficos de los pacientes adolescentes con deformidades angulares de los miembros pélvicos tratados con sistema de osteotomía en cuña abierta. MATERIAL Y MÉTODOS: Estudio observacional, prospectivo, analítico y transversal de los pacientes con diagnóstico de deformidad angular de los miembros pélvicos tratados con sistema de osteotomía en cuña abierta. Se valoraron mediante radiografía el ángulo femorotibial, el ángulo de desviación del eje mecánico (MAD), la discrepancia de miembros inferiores y los grados de centro de rotación de la deformidad (CORA) pre- y post­quirúrgico. Se realizó una encuesta telefónica de la escala funcional postquirúrgica IKDC 2000. RESULTADOS: Se valoraron 28 pacientes, 21 femeninos y siete masculinos, con un promedio de edad de intervención quirúrgica de 15.3 años. Sus diagnósticos: genu valgo idiopático, 10 casos; enfermedad de Blount, cuatro; tumoraciones benignas, tres; raquitismo hipofosfatémico, tres y otros como secuelas de artritis séptica de rodilla, hipoplasia femoral y secuelas de fractura. Fueron un total de 29 osteotomías: 17 de tibia y 12 de fémur; 17 osteotomías presentaban desviación lateral del eje mecánico, 11 desviación medial, con una media de ángulo femorotibial de 17 y 7.35 (p 0.03), respectivamente; la discrepancia inicial promedio tuvo una mejoría de 0.5 cm. El IKDC postquirúrgico en la evaluación subjetiva tuvo una media de 95.3 puntos. CONCLUSIONES: La fijación de osteotomías con placas de cuña abierta es una opción con buenos resultados tanto clínicos como radiográficos.

[Exposed distal radio-ulnar dislocation by dog bite. Reconstructive surgical technique using a soft tissue graft and a syndesmotic fixation implant. Case report]. / Luxación radio-cubital distal expuesta por mordedura canina no asociada con fractura. Técnica quirúrgica reconstructiva mediante anclaje para sindesmosis e injerto tendinoso. Reporte de caso.

The main function of the forearm is the supination, which is achieved largely through the biomechanical characteristics and stability of the distal radio-ulnar joint. There are several surgical techniques for the treatment of distal radio-ulnar dislocations isolated or associated with a fracture. We report the case of a canine trainer who was bitten at the wrist and distal forearm that came to the emergency department in where distal ulnar dislocation with muscle tendon exposure was diagnosed. Due to the offending agent and multiple soft tissue injuries the treatment with standard techniques was impossible. We describe the technique of treatment of this patient by placing autologous gracilis tendon graft, platelet rich plasma and two anchoring systems for ankle syndesmosis. Immobilization was maintained for six weeks with a subsequent rehabilitation and posterior valuation at 12, 18 and 28 weeks by the scale of MAYO, PRWE and DASH and finding a good result which implies the return to work and daily activities of the patient with minimal pain and limitation.

La función principal del antebrazo es la pronosupinación, la cual se logra en gran medida mediante la estabilidad y características biomecánicas de la articulación radio-cubital distal. Existen diversas técnicas quirúrgicas para el tratamiento de las luxaciones radio-cubitales distales aisladas o asociadas con fractura. Presentamos el caso de un paciente entrenador canino quien fue mordido a nivel de la muñeca y antebrazo distal acudiendo al Servicio de Urgencias en donde se diagnostica una luxación cubital distal con exposición músculo tendinosa. Debido al agente lesivo y las múltiples lesiones de partes blandas resultó imposible realizar las técnicas habituales de tratamiento. Se describe la técnica utilizada para el manejo de este paciente mediante la colocación de injerto tendinoso autólogo de gracilis, plasma rico en plaquetas y dos sistemas de anclaje para sindesmosis de tobillo. Se inmovilizó por seis semanas e inició rehabilitación subsecuente y valorándolo a las 12, 18 y 28 semanas mediante la escala de MAYO, DASH y PRWE encontrando un resultado bueno que implica la reincorporación a las actividades laborales y cotidianas del paciente con un mínimo dolor y limitación.

Nanoparticle-driven DNA damage mimics irradiation-related carcinogenesis pathways.

The epidemiological association between cancer and exposure to ambient air pollution particles (particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10))) has been related to the ability of PM(10) and its constituent nanoparticles (NPs) to cause reactive oxidative species (ROS)-driven DNA damage. However, there are no data on the molecular response to these genotoxic effects. In order to assess whether PM(10), NP and ROS-driven DNA damage induce carcinogenesis pathways, A549 cells were treated with tert-butyl-hyperperoxide (Tbh), urban dust (UD), carbon black (CB), nanoparticulate CB (NPCB), benzo(a)pyrene (BaP) and NPCB coated with BaP for

Soluble transition metals in welding fumes cause inflammation via activation of NF-kappaB and AP-1.

We previously reported that the molecular pro-inflammatory effects of welding fumes in vitro were caused by soluble transition metals via an oxidative stress-mediated mechanism. Herein, we tested the hypothesis that transition metals in welding fume drive the in vivo inflammatory response caused by welding fume. Rats were instilled with either whole, soluble extract or washed welding fume particulates or soluble extracts pre-treated with a transition metal chelator. Markers of pulmonary inflammation were measured in the bronchoalveolar lavage fluid (BALF) and nuclear translocation of transcription factor was assessed in BAL cells by electrophoretic mobility shift assay. Instillation of either whole or soluble fractions of welding fume caused a significant influx of inflammatory cells and other markers of inflammation in the BALF 24 h later. MIP-2 protein in BALF and nuclear translocation of NF-kappaB and AP-1 were significantly greater following instillation of whole and soluble fractions than in saline-instilled lungs. Chelation of the soluble fraction, to remove transition metals, abolished the ability to cause inflammation, MIP-2 increase or transcription factor translocation to the nucleus. Instillation of washed particulates alone caused no significant change in any end-point compared to saline. This study demonstrates that soluble transition metals present in welding fumes cause inflammation via activation of the redox-sensitive transcription factors NF-kappaB and AP-1 and confirms the validity of utilising in vitro models to assess inflammatory responses to such particles.

Calcium and ROS-mediated activation of transcription factors and TNF-alpha cytokine gene expression in macrophages exposed to ultrafine particles.

Ultrafine (Uf) particles are a component of particulate air pollution suggested to be responsible for the health effects associated with elevations of this pollutant. We have previously suggested that Uf particles, through the induction of oxidative stress, may induce inflammation in the lung, thus exacerbating preexisting illness in susceptible individuals. Alveolar macrophages are considered to play a key role in particlemediated inflammation and lung disease. The effect of Uf particles on rat alveolar macrophages and human blood monocytes was investigated with reference to the roles of calcium and reactive oxygen species (ROS). TNF-alpha protein release, intracellular calcium concentration, TNF-alpha mRNA expression, and transcription factor activation were studied as end points after treatment of rat alveolar macrophages or peripheral blood monocytes. The calcium channel blocker verapamil, the intracellular calcium chelator BAPTA-AM, the calmodulin inhibitor W-7, and the antioxidants Trolox and Nacystelin (NAL) were included in combination with Uf particles. Verapamil reduced intracellular calcium concentration in rat alveolar macrophages on stimulation with Uf particles. This effect was also apparent with transcription factor AP-1 activation. All antagonists and antioxidants reduced Uf-stimulated nuclear localization of the p50 and p65 subunits of NF-kappaB in human monocytes. Verapamil, BAPTA-AM, and NAL reduced Uf-stimulated TNF-alpha protein release, whereas only verapamil reduced Uf-stimulated mRNA expression in rat alveolar macrophages. In human monocytes, verapamil, Trolox, BAPTA-AM, and W-7 reduced Uf-stimulated TNF-alpha protein release. These findings suggest that Uf particles may exert proinflammatory effects by modulating intracellular calcium concentrations, activation of transcription factors, and cytokine production through a ROS-mediated mechanism.

PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha.

There is now considerable evidence for an association between the levels of particulate air pollution [particulate matter <10 microm in aerodynamic diameter (PM(10))] and various adverse health endpoints. The release of proinflammatory mediators from PM(10)-exposed macrophages may be important in stimulating cytokine release from lung epithelial cells, thus amplifying the inflammatory response. A549 cells were treated with conditioned media from monocyte-derived macrophages stimulated with PM(10), titanium dioxide (TiO(2)), or ultrafine TiO(2). We demonstrate that only conditioned media from PM(10)-stimulated macrophages significantly increased nuclear factor-kappaB and activator protein-1 DNA binding, enhanced interleukin-8 (IL-8) mRNA levels as assessed by RT-PCR, and augmented IL-8 protein levels, over untreated controls. Furthermore, PM(10)-conditioned media also caused transactivation of IL-8 as determined by an IL-8-chloramphenicol acetyl transferase reporter. Analysis of these conditioned media revealed marked increases in tumor necrosis factor-alpha (TNF-alpha) and protein levels and enhanced chemotactic activity for neutrophils. Preincubation of conditioned media with TNF-alpha-neutralizing antibodies significantly reduced IL-8 production. These data suggest that PM(10)-activated macrophages may amplify the inflammatory response by enhancing IL-8 release from lung epithelial cells, in part, via elaboration of TNF-alpha.

Persistent depletion of I kappa B alpha and interleukin-8 expression in human pulmonary epithelial cells exposed to quartz particles.

Chronic inflammation and fibrosis following quartz inhalation has been associated with persistent up-regulation of several "pro-inflammatory" genes, which are commonly regulated by nuclear factor kappa-B (NF-kappaB). Transcription of the NF-kappaB-inhibitor IkappaBalpha is also under NF-kappaB control, and its de novo synthesis is considered to comprise a negative feedback loop in transient inflammation. To investigate this mechanism in particle inflammation, we have studied IkappaBalpha degradation in A549 cells exposed to DQ12-quartz or TiO(2), in relation to the expression of IL-8. Although both quartz and TiO(2) were found to cause IkappaBalpha degradation, only quartz elicited a mild IkappaBalpha depletion, first appearing at 4 h. TiO(2) was found to cause a higher short-term increase in IkappaBalpha mRNA-expression compared to quartz, whereas the early enhancement of IL-8 expression and release was similar for both particles. Up-regulation of IL-8 expression was found to persist with quartz only. Cotreatment with PDTC and curcumin reduced particle-elicited IL-8 response, whereas cycloheximide caused enhancement of IL-8 mRNA expression in both the quartz- and TiO(2)-treated cells. Our results demonstrate that mineral dusts cause IkappaBalpha degradation, a transient increase in de novo synthesis of IkappaBalpha, and enhanced IL-8 expression in human pulmonary epithelial cells. While IkappaBalpha degradation and early IL-8 expression seem to be general particle phenomena, particle-specific characteristics impact on activation of IkappaBalpha gene transcription, apparently accounting for the different proinflammatory IL-8 responses seen with quartz and TiO(2) in the longer term. These observations may provide an explanation for the transient versus the persistent pulmonary inflammatory status and subsequent differences in pathogenic potency of TiO(2) and quartz.

Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation.

Exposure to particulate air pollution (PM(10)) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM(10) induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM(10), endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM(10) could activate nuclear factor-kappa B (NF-kappaB), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM(10) samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-kappaB in A549 cells. Furthermore, increased NF-kappaB activity was observed in the absence of IkappaB degradation. To evaluate the role of iron, A549 cells were exposed to PM(10) previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM(10) were able to activate NF-kappaB, whereas this response was completely abrogated in cells exposed to PM(10) treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM(10) on NF-kappaB activation by exposing alveolar epithelial cells to soluble fractions from PM(10) treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM(10) which activated NF-kappaB, fractions from PM(10) treated with deferoxamine and ferrozine did not stimulate NF-kappaB activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PM(10) did not inhibit NF-kappaB. In summary, PM(10) activates NF-kappaB in A549 cells by an iron-mediated mechanism in the absence of IkappaB degradation.

Apocynin increases glutathione synthesis and activates AP-1 in alveolar epithelial cells.

Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent intracellular inhibitor of superoxide anion production in neutrophils. In this study, we studied the effect of apocynin on the regulation of the antioxidant glutathione (GSH) and activation of the transcription factor AP-I in human alveolar epithelial cells (A549). Apocynin enhanced intracellular GSH by increasing gamma-glutamylcysteine synthetase activity in A549 cells. Apocynin also increased the expression of gamma-GCS heavy subunit mRNA. This was associated with increased AP-1 DNA binding as measured by the electrophoretic mobility shift assay. These data indicate that apocynin displays antioxidant properties, in part, by increasing glutathione synthesis through activation of AP-1.

Mechanisms of asbestos-induced nitric oxide production by rat alveolar macrophages in inhalation and in vitro models.

To evaluate the contribution of reactive nitrogen species to inflammation by asbestos, Fischer 344 rats were exposed to crocidolite or chrysotile asbestos by inhalation to determine whether increases occurred in nitric oxide (NO.) metabolites from alveolar macrophages (AMs). AMs from animals inhaling asbestos showed significant elevations (p < .05) in nitrite/nitrate levels which were ameliorated by NG-monomethyl-L-arginine (NMMA), an inhibitor of inducible nitric oxide synthase (iNOS) activity. Temporal patterns of NO. generation from AMs correlated with neutrophil influx in bronchoalveolar lavage samples after asbestos inhalation or bleomycin instillation, another model of pulmonary fibrosis. To determine the molecular mechanisms and specificity of iNOS promoter activation by asbestos, RAW 264.7 cells, a murine macrophage-like line, and AMs isolated from control rats were exposed to crocidolite asbestos in vitro. These cells showed increases in steady-state levels of iNOS mRNA in response to asbestos and more dramatic increases in both iNOS mRNA and immunoreactive protein after addition of lipopolysaccharide (LPS). After transfection of an iNOS promoter/luciferase reporter construct, RAW 264.7 cells exposed to LPS, crocidolite asbestos and its nonfibrous analog, riebeckite, revealed increases in luciferase activity whereas cristobalite silica had no effects. Studies suggest that NO. generation may be important in cell injury and inflammation by asbestos.

Comparative value of thallium and glucose SPECT imaging in childhood brain tumors.

Thallium-201 chloride (201Tl) single-photon emission computed tomography (SPECT) detects a high percentage of histologically and anatomically diverse pediatric brain tumors. Thallium-201 chloride SPECT and F-18 fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) are the most commonly used radionuclide techniques in neuro-oncology. Having developed a methodology to image 18F-FDG with SPECT, the authors performed SPECT scans coupled with magnetic resonance imaging to assess the comparative sensitivity of 201Tl and 18F-FDG in 19 children with brain tumors. Tumors were detected using 201Tl SPECT in 14 of 19 patients. Five of five postoperative residual tumors were detected by 201Tl SPECT, and six of seven after irradiation recurrences were detected. F-18 fluoro-deoxy-glucose SPECT detected tumors in only three of 19 patients, all of whom had abnormal 201Tl studies (all three after therapy recurrences). Thallium-201 chloride SPECT could be interpreted in 18 of 19 patients without magnetic resonance imaging confirmation, but none of the 19 18F-FDG SPECT studies could be interpreted without magnetic resonance imaging. Thallium-201 chloride SPECT is more sensitive than 18F-FDG SPECT in the detection of primary or recurrent childhood brain tumors. The failure of 18F-FDG SPECT in follow-up after therapy is primarily a problem of limited fluoro-deoxy-glucose uptake, not spatial resolution. Thallium-201 chloride SPECT is a promising imaging modality in neuro-oncology.

Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2.

Stimulation of cell signaling cascades by oxidants may be important in the pathogenesis of pulmonary and pleural diseases. Here, we demonstrate in rat pleural mesothelial cells that apoptotic concentrations of crocidolite asbestos and H2O2 induce phosphorylation and activation of extracellular signal-regulated protein kinases (ERK). Activation of c-jun-NH2-terminal protein kinases (JNK)/stress-activated protein kinases was also observed in response to H2O2. In contrast, asbestos caused more protracted activation of ERK without JNK activation. Both H2O2- and asbestos-induced activation of ERK was abolished by catalase. Moreover, chelation of surface iron from crocidolite fibers or addition of N-acetyl-L-cysteine prevented ERK activation and apoptosis by crocidolite, indicating an oxidative mechanism of cell signaling. The MEK1 inhibitor PD-98059 abrogated asbestos-induced apoptosis, confirming a causal relationship between ERK activation and apoptosis. These results suggest that distinct cell-signaling cascades may be important in phenotypic responses elicited by oxidant stresses.

Cell signaling pathways elicited by asbestos.

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.

Novel cell imaging techniques show induction of apoptosis and proliferation in mesothelial cells by asbestos.

We developed in situ dual-fluorescence detection techniques for measuring apoptosis and proliferation simultaneously in single dishes of cells. The deoxyribonucleic acid (DNA)-specific labeling method, terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), first was used in conjunction with a 4',6-diamidino-2-phenylindole (DAPI) counterstain to detect and measure morphologic characteristics of apoptotic rat pleural mesothelial (RPM) cells isolated from Fischer 344 rats and exposed to 300 microM hydrogen peroxide (H2O2). For this purpose, 100 TUNEL-positive nuclei were measured while being viewed with DAPI counterstaining for area, perimeter, longest diameter, and average diameter, using imaging software and an image-collection apparatus. We then exposed cells to a range of concentrations of crocidolite asbestos and putative apoptotic and mitogenic agents. Exposure to crocidolite asbestos (5 microg/cm2) caused a striking dose-dependent apoptotic response at 24 h, 48 h, and 72 h. The nonfibrous crocidolite analogue riebeckite failed to induce apoptosis. At 24 h, tumor necrosis factor-alpha (TNF-alpha) (10 ng/ml) caused an increase in apoptotic nuclei. A second method, utilizing an antibody to 5'-bromodeoxyridine (BrdU) and oxazole yellow homodimer (YOYO), showed a dose-dependent increase in proliferation occurring in cells exposed to asbestos (5 microg/cm2) at 48 h and 72 h. In addition, increased numbers of rat pleural mesothelial (RPM) cells exposed to 12-O-tetradecanoylphorbol-13-acetate (TPA), TNF-alpha, and epidermal growth factor (EGF) exhibited incorporation of BrdU at these time points, although total numbers of cells per unit area were unchanged. Results indicate a dynamic balance between apoptosis and increased DNA synthesis after exposure of mesothelial cells to asbestos.