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2.
Cad. saúde pública ; 31(3): 517-530, 03/2015. tab, graf
Artículo en Inglés | LILACS | ID: lil-744825

RESUMEN

A territorial analysis of Aedes aegypti density was conducted in two Colombian cities using an ecosystem and chorematic approach. Entomological and behavioral data (by cluster) and information on the urban context were used to analyze the relationship between territorial structures and dynamics and vector density. The results were represented in graphic (chorematic) models. Arauca showed higher vector density than Armenia. Higher density was related to unplanned urbanization, flood-prone areas, low socioeconomic strata, household water tanks, higher temperature, and recall of control measures for adult mosquitos. Zones with low density indices coincided with diverse socioeconomic, ecological, and behavioral conditions. The study found a relationship between territorial structures and dynamics and vector density in both Arauca and Armenia, where the interaction between ecological and social systems shape areas with high and low A. aegypti density.


Foi realizada uma análise territorial da densidade do Aedes aegypti em duas cidades da Colômbia, desde um enfoque ecossistêmico e da coremática. Com base em informação entomológica e comportamental (por conglomerados) e informação do contexto urbano, foi indagada a relação de estruturas dinâmicas do território com a densidade vetorial. Foram apresentados os resultados com modelos gráficos (coremática). Identificou-se maior densidade vetorial em Arauca do que na Armênia. Maiores densidades foram relacionadas à urbanização não planejada, zonas de alagamento, estratos socioeconômicos baixos, tanques baixos (reservatórios), maior temperatura e relatório de ações contra os mosquitos adultos. Zonas de densidades baixas coincidiram com diversas condições socioeconômicas, ecológicas e comportamentais. Foi encontrada uma relação das estruturas e dinâmicas do território com a densidade vetorial para Arauca e Armênia, onde a interação entre sistemas ecológicos e sociais configura zonas particulares de alta e baixa densidades de A. aegypti.


Se realizó un análisis territorial de la densidad de Aedes aegypti en dos ciudades de Colombia desde un enfoque ecosistémico y la coremática. A partir de información entomológica y comportamental (por conglomerados) e información del contexto urbano, se indagó la relación de estructuras y dinámicas del territorio con la densidad vectorial. Se representaron los resultados con modelos gráficos (coremática). Se identificó mayor densidad vectorial en Arauca que en Armenia. Mayores densidades se relacionaron con urbanización no planeada, zonas de inundación, estratos socioeconómicos bajos, tanques bajos (alberca), mayor temperatura y reporte de acciones hacia los mosquitos adultos. Zonas de densidades bajas coincidieron con diversas condiciones socioeconómicas, ecológicas y comportamentales. Se encontró relación de las estructuras y dinámicas del territorio con la densidad vectorial para Arauca y Armenia, donde la interacción entre sistemas ecológicos y sociales configuran zonas particulares de alta y baja densidad de A. aegypti.


Asunto(s)
Animales , Ratas , Apoptosis/efectos de los fármacos , Benzamidas/farmacología , Inhibidores Enzimáticos/farmacología , Ácidos Grasos no Esterificados/farmacología , Células Secretoras de Insulina/enzimología , Fenantrenos/farmacología , Poli(ADP-Ribosa) Polimerasas/biosíntesis , Línea Celular , Regulación hacia Abajo/efectos de los fármacos , Proteínas de Homeodominio/biosíntesis , Insulina , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Transactivadores/biosíntesis
3.
Rev. méd. Chile ; 143(2): 147-157, feb. 2015. graf, tab
Artículo en Español | LILACS | ID: lil-742565

RESUMEN

Background: There is a gap between the number of patients requiring a renal allograft and the number of potential deceased donors (DD). One alternative is using allografts from non-related living donors (NRLD). Aim: To compare survival and complications of renal allograft recipients from DD, related living donors (RLD) and NRLD. Material and Methods: Observational study of a cohort of renal allograft recipients. Of 253 transplants performed in a Chilean region between 1981 and 2003, 20 patients received and allograft from a NRLD. Graft and patient survival of these patients were compared with those of 93 patients receiving an allograft from a related living donor and 140 receiving it from a DD. Patients were followed for 10 years or until death or dialysis requirement. Results: No significant differences between groups in graft and patient survival, deaths with a functioning graft or return to dialysis were observed. Receptors of DD had more hospital admissions during the first years after receiving the graft, usually due to infections. Also a delayed graft function was more common among them. Glomerular filtration rate ten years after the graft was similar among the three groups. Conclusions: No differences in graft or patient survival was observed between patients receiving a renal allograft from NRLD, RLD or DD.


Asunto(s)
Animales , Femenino , Ratones , Ratas , Analgésicos , Antiinflamatorios no Esteroideos , Niacinamida/análogos & derivados , Niacinamida/farmacología , Amidas/farmacología , Carragenina , Dipirona/farmacología , Edema/inducido químicamente , Edema/tratamiento farmacológico , Formaldehído , Calor , Isomerismo , Actividad Motora/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Ácidos Picolínicos/farmacología , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Equilibrio Postural/efectos de los fármacos , Ratas Wistar
4.
Rev. bras. cir. cardiovasc ; 30(1): VI-VII, Jan-Mar/2015. graf
Artículo en Inglés | LILACS | ID: lil-742894
5.
Rev. bras. cir. cardiovasc ; 30(1): 70-76, Jan-Mar/2015. tab, graf
Artículo en Inglés | LILACS | ID: lil-742901

RESUMEN

Objective: An unclear issue is whether gender may influence at cardiac remodeling after myocardial infarction (MI). We evaluated left ventricle remodeling in female and male rats post-MI. Methods: Rats were submitted to anterior descending coronary occlusion. Echocardiographic evaluations were performed on the first and sixth week post-occlusion to determine myocardial infarction size and left ventricle systolic function (FAC, fractional area change). Pulsed Doppler was applied to analyze left ventricle diastolic function using the following parameters: E wave, A wave, E/A ratio. Two-way ANOVA was applied for comparisons, complemented by the Bonferroni test. A P≤=0.05 was considered significant. Results: There were no significant differences between genders for morphometric parameters on first (MI [Female (FE): 44.0±5.0 vs. Male (MA): 42.0±3.0%]; diastolic [FE: 0.04±0.003 vs. MA: 0.037±0.005, mm/g] and systolic [FE: 0.03±0.0004 vs. MA: 0.028±0.005, mm/g] diameters of left ventricle) and sixth (MI [FE: 44.0±5.0 vs. MA: 42.0±3.0, %]; diastolic [FE: 0.043±0.01 vs. MA: 0.034±0.005, mm/g] and systolic [FE: 0.035±0.01 vs. MA: 0.027±0.005, mm/g] of LV) week. Similar findings were reported for left ventricle functional parameters on first (FAC [FE: 34.0±6.0 vs. MA: 32.0±4.0, %]; wave E [FE: 70.0±18.0 vs. MA: 73.0±14.0, cm/s]; wave A [FE: 20.0±12.0 vs. MA: 28.0±13.0, cm/s]; E/A [FE: 4.9±3.4 vs. MA: 3.3±1.8]) and sixth (FAC [FE: 29.0±7.0 vs. MA: 31.0±7.0, %]; wave E [FE: 85.0±18.0 vs. MA: 87.0±20.0, cm/s]; wave A [FE: 20.0±11.0 vs. MA: 28.0±17.0, cm/s]; E/A [FE: 6.2±4.0 vs. MA: 4.6±3.4]) week. Conclusion: Gender does not influence left ventricle remodeling post-MI in rats. .


Objetivo: A influência do gênero no remodelamento cardíaco após o infarto do miocárdio é uma questão em intenso debate. Nós avaliamos o remodelamento ventricular esquerdo em ratos infartados de ambos os gêneros. Métodos: O infarto do miocárdio foi induzido por oclusão da artéria coronária descendente anterior (fêmeas [FM]; machos [MC]). A ecocardiografia foi realizada na primeira e sexta semana pós-oclusão para determinar o tamanho do infarto do miocárdio e a função sistólica do ventricular esquerdo (mudança na área fracional [FAC]). A função diastólica derivou dos seguintes parâmetros: onda E; onda A; razão E/A. ANOVA duas vias com pós-teste de Bonferroni foi aplicado nas comparações (P≤=0,05). Resultados: Todas variáveis morfométricas foram similares (P>0,05) entre os gêneros com uma (infarto do miocárdio [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,04±0,003 vs. MC: 0,037±0,005, mm/g] e sistólico [FM: 0,03±0,0004 vs. MC: 0,028±0,005, mm/g] do VE) e seis (IM [FM: 44,0±5,0 vs. MC: 42,0±3,0, %]; diâmetro diastólico [FM: 0,043±0,01 vs. MC: 0,034±0,005, mm/g] e sistólico [FM: 0,035±0,01 vs. MC: 0,027±0,005, mm/g] do ventricular esquerdo) semanas. Achado similar ocorreu para os dados funcionais com uma (FAC [FM: 34,0±6,0 vs. MC: 32,0±4,0, %]; onda E [FM: 70,0±18,0 vs. MC: 73,0±14,0, cm/s]; onda A [FM: 20,0±12,0 vs. MC: 28,0±13,0, cm/s]; E/A [FM: 4,9±3,4 vs. MC: 3,3±1,8]) e seis (FAC [FM: 29,0±7,0 vs. MC: 31,0±7,0, %]; onda E [FM: 85,0±18,0 vs. MC: 87,0±20,0, cm/s]; onda A [FM: 20,0±11,0 vs. MC: 28,0±17,0 cm/s]; E/A [FM: 6,2±4,0 vs. MC: 4,6±3,4]) semanas. Conclusão: O gênero não é determinante para o remodelamento ventricular esquerdo pós-infarto do miocárdio em ratos. .


Asunto(s)
Animales , Humanos , Recién Nacido , Ratas , Enterocolitis Necrotizante/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Mucosa Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Niacinamida/farmacología , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Análisis de Varianza , Animales Recién Nacidos , Muerte Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Activación Enzimática , Enterocolitis Necrotizante/enzimología , Enterocolitis Necrotizante/patología , Mucosa Intestinal/enzimología , Mucosa Intestinal/patología , Intestinos/enzimología , Intestinos/patología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas Sprague-Dawley , Tirosina/análogos & derivados , Tirosina/metabolismo
6.
ABCD (São Paulo, Impr.) ; 28(1): 81-85, 2015.
Artículo en Inglés | LILACS | ID: lil-742753

RESUMEN

INTRODUCTION: The surgeon's formation process has changed in recent decades. The increase in medical schools, new specialties and modern technologies induce an overhaul of medical education. Medical residency in surgery has established itself as a key step in the formation of the surgeon, and represents the ideal and natural way for teaching laparoscopy. However, the introduction of laparoscopic surgery in the medical residency programs in surgical specialties is insufficient, creating the need for additional training after its termination. OBJECTIVE: To review the surgical teaching ways used in services that published their results. METHODS: Survey of relevant publications in books, internet and databases in PubMed, Lilacs and Scielo through july 2014 using the headings: laparoscopy; simulation; education, medical; learning; internship and residency. RESULTS: The training method for medical residency in surgery focused on surgical procedures in patients under supervision, has proven successful in the era of open surgery. However, conceptually turns as a process of experimentation in humans. Psychomotor learning must not be developed directly to the patient. Training in laparoscopic surgery requires the acquisition of psychomotor skills through training conducted initially with surgical simulation. Platforms based teaching problem solving as the Fundamentals of Laparoscopic Surgery, developed by the American Society of Gastrointestinal Endoscopic Surgery and the Laparoscopic Surgical Skills proposed by the European Society of Endoscopic Surgery has been widely used both for education and for the accreditation of surgeons worldwide. CONCLUSION: The establishment of a more appropriate pedagogical process for teaching laparoscopic surgery in the medical residency programs is mandatory in order to give a solid surgical education and to determine a structured and safe professional activity. .


INTRODUÇÃO: A formação do cirurgião geral vem se modificando nas últimas décadas. O aumento das escolas médicas, as novas especialidades e as modernas tecnologias induzem à reformulação do ensino médico. A residência médica em cirurgia estabeleceu-se como etapa fundamental na formação do cirurgião e surge como a forma ideal e natural para o ensino da videocirurgia. No entanto, a introdução da videocirurgia nos programas de residência médica nas diversas especialidades cirúrgicas é insuficiente, gerando a necessidade de treinamento complementar após o seu término. OBJETIVO: Rever a situação de ensino da videocirurgia em serviços que publicaram seus métodos. MÉTODO: Revisão de conteúdo publicado em livros e na internet considerados relevantes, além de pesquisa nas bases de dados PubMed, Lilacs e Scielo até julho 2014 com os descritores: videocirurgia; simulação; educação médica; aprendizagem; treinamento em cirurgia. RESULTADO: O método de treinamento em programas de residência médica em cirurgia, focado na realização de procedimentos cirúrgicos sob supervisão em pacientes, comprovou sua eficiência na era da cirurgia aberta. No entanto, configura conceitualmente um processo de experimentação em seres humanos. O aprendizado psicomotor não deve e não pode ser desenvolvido diretamente no paciente. A formação em videocirurgia requer a aquisição de habilidades psicomotoras únicas, através de treinamento realizado inicialmente por simulação cirúrgica. Plataformas de ensino baseadas na solução de problemas como o Fundamentals of Laparoscopic Surgery, desenvolvido pela Sociedade Americana de Cirurgia Endoscópica Gastrointestinal e o Laparoscopic Surgical Skills proposto pela Sociedade Europeia de Cirurgia Endoscópica são exemplos que têm sido amplamente utilizados tanto para o ensino como para a acreditação de cirurgiões em todo o mundo. CONCLUSÃO: É necessário o estabelecimento de um processo pedagógico mais adequado para o ensino da videocirurgia ...


Asunto(s)
Animales , Humanos , Ratones , Ratas , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Óxidos de Nitrógeno/farmacología , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Antioxidantes/química , Línea Celular , Espectroscopía de Resonancia por Spin del Electrón , Inhibidores Enzimáticos/química , Enlace de Hidrógeno , Óxidos de Nitrógeno/química
7.
ABCD (São Paulo, Impr.) ; 28(1): 20-23, 2015. tab
Artículo en Inglés | LILACS | ID: lil-742758

RESUMEN

BACKGROUND: Gastroesophageal reflux disease is an increasingly common condition worldwide causing a considerable economic impact. More than half the patients with clinical symptoms of reflux disease display no mucosal erosions on esophagogastroduodenoscopy, making it impossible to confirm the diagnosis without further investigations. AIM: To evaluate the correlation between minimal endoscopic changes on white-light esophagogastroduodenoscopy (carditis, mucosal thickening and invisibility of vessels) and histologic changes observed in distal esophageal biopsies in a sample of patients with symptoms suggestive of reflux disease, and to verify the specificity of these symptoms for non-erosive reflux disease. METHODS: Retrospective, cross-sectional study based on information retrieved from a digital database at a Brazilian hospital for the period March-October, 2012. The sample consisted of previously untreated, non-smoking subjects aged >18 years with symptoms suggestive of reflux disease but no esophageal erosions, submitted to esophagogastroduodenoscopy and distal esophageal biopsy. RESULTS: The final sample included 23 subjects. The most frequently observed change was invisibility of vessels (n=21; 91.3%), followed by mucosal thickening (n=15; 65.2%) and carditis (n=5; 21.7%). The correlation coefficient between each variable and the anatomopathological diagnosis was 0.386 for body mass index, 0.479 for mucosal thickening, -0.116 for invisibility of vessels, 0.306 for carditis and 0.462 for hiatal hernia. CONCLUSION: All patients displayed minimal endoscopic changes on esophagogastroduodenoscopy, but only mucosal thickening revealed a moderately significant correlation with severity of esophagitis, although increased body mass index values and the presence of hiatal hernia were also associated. .


RACIONAL: Doença do refluxo gastroesofágico é condição cada vez mais comum em todo o mundo causando impacto econômico considerável. Mais da metade dos pacientes com sintomas clínicos da doença não apresentam erosões endoscópicas da mucosa, o que torna impossível confirmar o diagnóstico sem outras investigações. OBJETIVO: Avaliar a correlação entre mudanças mínimas endoscópicas em endoscopia digestiva alta de luz branca (cardite, espessamento da mucosa e invisibilidade de vasos) e as alterações histológicas observadas em biópsias distais de uma amostra de pacientes com sintomas sugestivos de doença do refluxo, e para verificar a especificidade desses sintomas para a doença não-erosiva. MÉTODOS: Estudo retrospectivo, transversal, com base em informações obtidas a partir de uma base de dados digital em um hospital brasileiro no período de março/outubro de 2012. A amostra foi composta por indivíduos não tratados previamente, não fumantes, >18 anos, com sintomas sugestivos de doença do refluxo, mas sem erosões esofágicas submetidos à endoscopia digestiva alta e biópsia de esôfago distal. RESULTADOS: A amostra final incluiu 23 indivíduos. A alteração mais frequente foi invisibilidade dos vasos (n=21; 91,3%), seguido por espessamento de mucosa (n=15; 65,2%) e cardite (n=5; 21,7%). O coeficiente de correlação entre cada variável e o diagnóstico anatomopatológico foi 0,386 para o índice de massa corporal, 0,479 para espessamento de mucosa, -0,116 para a invisibilidade de vasos, 0,306 para carditis e 0,462 para hérnia hiatal. CONCLUSÃO: Todos os pacientes apresentaram alterações endoscópicas mínimas, mas apenas espessamento da mucosa revelou correlação moderadamente significativa com a gravidade da esofagite, apesar do aumento dos valores no índice de massa corporal e da presença de hérnia hiatal também estarem associados. .


Asunto(s)
Animales , Masculino , Ratas , Isquemia Encefálica/tratamiento farmacológico , Isoquinolinas/farmacología , Neutrófilos/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Isquemia Encefálica/fisiopatología , Roturas del ADN , Modelos Animales de Enfermedad , Radicales Libres/metabolismo , Mediciones Luminiscentes , Neutrófilos/metabolismo , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/fisiopatología , Factores de Tiempo
8.
The Korean Journal of Gastroenterology ; : 147-154, 2013.
Artículo en Coreano | WPRIM | ID: wpr-143723

RESUMEN

Pancreatic ductal adenocarcinoma is one of the most dreaded malignancies and the 5th leading cause of cancer-related death in Korea. Late diagnosis and unfavorable response to both chemotherapy and radiotherapy result in exceptionally poor prognosis. Recently, the rapid advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis, and there are many attempts to modulate signal pathway using specific targeted agent. However, the most of them have so far failed to improve survival significantly except erlotinib. The real challenge is now how these impressive advances of molecular biology could be successfully integrated into better clinical implications. Herein, we summarize the latest insights into the carcinogenesis, and their repercussions for novel targeted agents for pancreatic cancer, and provide a review of recent clinical trials using molecular targeted therapy.


Asunto(s)
Humanos , Antineoplásicos/uso terapéutico , Epigénesis Genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Terapia Molecular Dirigida , Neoplasias Pancreáticas/tratamiento farmacológico , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Receptores ErbB/antagonistas & inhibidores , Receptor IGF Tipo 1/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
9.
The Korean Journal of Gastroenterology ; : 147-154, 2013.
Artículo en Coreano | WPRIM | ID: wpr-143714

RESUMEN

Pancreatic ductal adenocarcinoma is one of the most dreaded malignancies and the 5th leading cause of cancer-related death in Korea. Late diagnosis and unfavorable response to both chemotherapy and radiotherapy result in exceptionally poor prognosis. Recently, the rapid advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis, and there are many attempts to modulate signal pathway using specific targeted agent. However, the most of them have so far failed to improve survival significantly except erlotinib. The real challenge is now how these impressive advances of molecular biology could be successfully integrated into better clinical implications. Herein, we summarize the latest insights into the carcinogenesis, and their repercussions for novel targeted agents for pancreatic cancer, and provide a review of recent clinical trials using molecular targeted therapy.


Asunto(s)
Humanos , Antineoplásicos/uso terapéutico , Epigénesis Genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Terapia Molecular Dirigida , Neoplasias Pancreáticas/tratamiento farmacológico , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , Receptores ErbB/antagonistas & inhibidores , Receptor IGF Tipo 1/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
10.
Yonsei Medical Journal ; : 862-869, 2006.
Artículo en Inglés | WPRIM | ID: wpr-141739

RESUMEN

Our experiments aimed to clarify the mechanism by which host cell apoptosis is inhibited by infection with the intracellular protozoan parasite, Toxoplasma gondii (T. gondii). Mouse spleen cells were cultured in 6-well plates with RPMI 1640/ 10% FBS at 37(i)E, in a 5% CO2 atmosphere. Apoptosis of spleen cells was induced by actinomycin-D (AD) treatment for 1 h prior to infection with T. gondii. A variety of assays were used to assess the progression of apoptosis: DNA size analysis on agarose gel electrophoresis, flow cytometry with annexin V/PI staining, and analysis of expression levels of Bcl-2 family and NF-kappaB mRNA and proteins by RT-PCR, Western blotting, and EMSA. Additionally, transmission electron microscopy (TEM) was performed to observe changes in cell morphology. Fragmentation of DNA was inhibited in spleen cells treated with AD and T. gondii 5 h and 18 h post infection, respectively, and flow cytometry studies showed a decreased apoptotic rates in AD and T. gondii treated spleen cells. We observed decreased expression of Bax mRNA and protein, while levels of Bcl-2 mRNA remained constant in spleen cells treated with AD and T. gondii. Caspase 3 and PARP were inactivated in cells treated with AD and T. gondii, and increased levels of cleaved caspase 8 were also observed. Analysis of EMSA and Western blot data suggests that activation of transcription factor NF-kappaB may be involved in the blockade of apoptosis by T. gondii. TEM analysis showed nuclear fragmentation and chromatin condensation occurring in spleen cells treated with AD; however, such apoptosis- associated morphological changes were not observed in cells treated with both AD and T. gondii tachyzoites. Together, these data show that T. gondii infection inhibits AD induced apoptosis via caspase inactivation and NF-kappaB activation in mouse spleen cells.


Asunto(s)
Ratones , Animales , Proteína X Asociada a bcl-2/metabolismo , Toxoplasma/fisiología , ARN Mensajero/metabolismo , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , FN-kappa B/metabolismo , Regulación de la Expresión Génica , Citometría de Flujo , Fragmentación del ADN , Células Cultivadas , Caspasa 3/antagonistas & inhibidores , Apoptosis/fisiología
11.
Yonsei Medical Journal ; : 862-869, 2006.
Artículo en Inglés | WPRIM | ID: wpr-141738

RESUMEN

Our experiments aimed to clarify the mechanism by which host cell apoptosis is inhibited by infection with the intracellular protozoan parasite, Toxoplasma gondii (T. gondii). Mouse spleen cells were cultured in 6-well plates with RPMI 1640/ 10% FBS at 37(i)E, in a 5% CO2 atmosphere. Apoptosis of spleen cells was induced by actinomycin-D (AD) treatment for 1 h prior to infection with T. gondii. A variety of assays were used to assess the progression of apoptosis: DNA size analysis on agarose gel electrophoresis, flow cytometry with annexin V/PI staining, and analysis of expression levels of Bcl-2 family and NF-kappaB mRNA and proteins by RT-PCR, Western blotting, and EMSA. Additionally, transmission electron microscopy (TEM) was performed to observe changes in cell morphology. Fragmentation of DNA was inhibited in spleen cells treated with AD and T. gondii 5 h and 18 h post infection, respectively, and flow cytometry studies showed a decreased apoptotic rates in AD and T. gondii treated spleen cells. We observed decreased expression of Bax mRNA and protein, while levels of Bcl-2 mRNA remained constant in spleen cells treated with AD and T. gondii. Caspase 3 and PARP were inactivated in cells treated with AD and T. gondii, and increased levels of cleaved caspase 8 were also observed. Analysis of EMSA and Western blot data suggests that activation of transcription factor NF-kappaB may be involved in the blockade of apoptosis by T. gondii. TEM analysis showed nuclear fragmentation and chromatin condensation occurring in spleen cells treated with AD; however, such apoptosis- associated morphological changes were not observed in cells treated with both AD and T. gondii tachyzoites. Together, these data show that T. gondii infection inhibits AD induced apoptosis via caspase inactivation and NF-kappaB activation in mouse spleen cells.


Asunto(s)
Ratones , Animales , Proteína X Asociada a bcl-2/metabolismo , Toxoplasma/fisiología , ARN Mensajero/metabolismo , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores , FN-kappa B/metabolismo , Regulación de la Expresión Génica , Citometría de Flujo , Fragmentación del ADN , Células Cultivadas , Caspasa 3/antagonistas & inhibidores , Apoptosis/fisiología
12.
Mem. Inst. Oswaldo Cruz ; 100(supl.1): 29-37, Mar. 2005. ilus
Artículo en Inglés | LILACS | ID: lil-402173

RESUMEN

Recent work has demonstrated that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron-transport chain triggers several pathways of injury [(protein kinase C (PKC), hexosamine and polyol pathway fluxes, advanced glycation end product formation (AGE)] involved in the pathogenesis of diabetic complications by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Increased oxidative and nitrosative stress activates the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP). PARP activation, on one hand, depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport and ATP formation. On the other hand, PARP activation results in inhibition of GAPDH by poly-ADP-ribosylation. These processes result in acute endothelial dysfunction in diabetic blood vessels, which importantly contributes to the development of various diabetic complications. Accordingly, hyperglycemia-induced activation of PKC and AGE formation are prevented by inhibition of PARP activity. Furthermore, inhibition of PARP protects against diabetic cardiovascular dysfunction in rodent models of cardiomyopathy, nephropathy, neuropathy, and retinopathy. PARP activation is also present in microvasculature of human diabetic subjects. The present review focuses on the role of PARP in diabetic complications and emphasizes the therapeutic potential of PARP inhibition in the prevention or reversal of diabetic complications.


Asunto(s)
Animales , Humanos , Daño del ADN , Complicaciones de la Diabetes/etiología , Estrés Oxidativo/fisiología , Ácido Peroxinitroso/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Complicaciones de la Diabetes/metabolismo , Activación Enzimática , Poli(ADP-Ribosa) Polimerasas/antagonistas & inhibidores
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