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2.
Int J Public Health ; 69: 1606736, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660497

RESUMO

Objective: Gender as the "sociocultural role of sex" is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors' consequences and inequalities men/women. We aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both? Methods: We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables. Results: We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term "gender" to define exposure. One article defined its "sex" exposure variable as gender-related mechanisms, and two articles used "sex" and "gender" interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors. Conclusion: Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.


Assuntos
Neoplasias Colorretais , Países Desenvolvidos , Humanos , Neoplasias Colorretais/epidemiologia , Masculino , Feminino , Fatores Sexuais , Incidência , Fatores de Risco , Países Desenvolvidos/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Fatores Socioeconômicos
3.
Eur J Cancer Care (Engl) ; 31(6): e13654, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35866619

RESUMO

OBJECTIVES: We studied both the independent and combined effects of the places of biopsy and treatment on the treatment time interval based on a population-based study. METHODS: We analysed the proportion of patients having a treatment time interval higher than the EUSOMA recommendation of 6 weeks, as a function of the number and the type of care centres the patients attended, from a French population-based regional cohort of women treated in 2015 for an incident invasive non-metastatic cancer (n = 505). RESULTS: About 33% [95% CI: 27; 38] of patients had a treatment time interval higher than 6 weeks. About 48% of the patients underwent their biopsy and their initial treatment in the different centres. Results from multivariable analyses supported the impact of the type and number of centres attended on the proportion of time intervals over 6 weeks. This proportion was higher among patients with biopsy and treatment in different centres and among patients treated in a university hospital. CONCLUSION: We pointed out the independent impact of the type and the number of care centres the patients attended, from biopsy to first treatment, on the treatment time interval, which is a well-known prognosis factor.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Biópsia
4.
rev. cuid. (Bucaramanga. 2010) ; 9(3): 2369-2378, sep.-dic. 2018. tab
Artigo em Espanhol | LILACS, BDENF, COLNAL | ID: biblio-979571

RESUMO

Resumen Introducción En la población adolescente la calidad de amistad se asocia con el desarrollo de conductas protectoras, no obstante es escasa la investigación que ha sido realizada para determinar si la percepción de la calidad de amistad es determinante en el consumo de alcohol, por tal motivo los objetivos del presente estudio fueron determinar la prevalencia global, lápsica, actual e instantánea de consumo de alcohol, identificar las diferencias de la calidad de amistad por tipo de consumo e identificar la relación entre la calidad de amistad y el consumo de consumo de alcohol de los adolescentes de bachillerato de una institución pública del estado de Nuevo León. Materiales y Métodos Estudio descriptivo correlacional, el tamaño de la muestra total fue de 308 adolescentes de bachillerato con un muestreo aleatorio estratificado con asignación proporcional al tamaño del estrato. Se utilizó la Escala de Calidad de Amistad y el Cuestionario de Identificación de los Trastornos debidos al Consumo de Alcohol. Resultados Los participantes del presente estudio contaron con una edad promedio de 15 años, se encontraron diferencias significativas entre los tipos de consumo de alcohol y la calidad de amistad (H= 7.06, p=.029), se encontró una relación negativa y significativa entre la calidad de amistad y el consumo de alcohol (rs=-.206, p<.01). Discusión y Conclusiones Se observó que las relaciones con mayor calidad de amistad reflejan menor consumo de alcohol en los adolescentes de bachillerato.


Abstract Introduction In the adolescent population, the quality of friendship is associated with the development of protective behaviors, but little research has been done to determine whether the perception of the quality of friendship is a determinant in alcohol consumption or not. For this reason, the objectives of this study were to determine the overall, lapsic, current and instantaneous prevalence of alcohol consumption, to identify the differences in the quality of friendship by type of consumption, and to identify the relationship between the quality of friendship and alcohol consumption of high school adolescents in a public institution in the state of Nuevo León. Materials and Methods A correlational descriptive study was conducted; the total sample size was 308 high school adolescents with a stratified random sample with proportional allocation to stratum size. The Friendship Quality Scale and the Alcohol Use Disorder Identification Questionnaire were used. Results Participants in this study were on average 15 years old. Significant differences were found between types of alcohol consumption and quality of friendship (H=7.06, p=.029); a negative and significant relationship was found between quality of friendship and alcohol consumption (rs = -.206, p<.01). Discussion and Conclusions Higher quality friend relationships were found to reflect lower alcohol consumption in high school adolescents.


Resumo Introdução Na população adolescente, a qualidade da amizade está associada com o desenvolvimento de condutas protetoras, no entanto, a pesquisa nesse sentido tem sido pouca para determinar se a percepção da qualidade da amizade é determinante no consumo de álcool. Por isso, os objetivos da presente pesquisa são determinar a prevalência global, lápsica, atual e instantânea do consumo de álcool; e, identificar as diferenças da qualidade da amizade por tipo de consumo de álcool nos adolescentes de ensino secundário de uma escola pública do estado de Nuevo León. Materiais e Métodos Pesquisa descritiva correlacional — o tamanho total da amostra foi de 308 adolescentes do ensino secundário, com uma amostragem aleatória estratificada e atribuição proporcional ao tamanho do estrato. Foi utilizada a Escala de Qualidade da Amizade, bem como o Questionário de Identificação dos Transtornos provocados pelo Consumo de Álcool. Resultados Os participantes da presente pesquisa tinham uma idade média de 15 anos e neles foram encontradas diferenças significativas em relação aos tipos de consumo de álcool e a qualidade da amizade (Hz 7,06, .029), foi evidenciada uma relação negativa e significativa entre a qualidade da amizade e o consumo de álcool (rs= -.206, P<.OI). Discussão e Conclusões Observou-se que as relações de maior qualidade da amizade pressupõem um consumo menor de álcool nos adolescentes do ensino secundário.


Assuntos
Humanos , Masculino , Feminino , Amigos , Consumo de Bebidas Alcoólicas , Adolescente , Relações Interpessoais
5.
PLoS Negl Trop Dis ; 12(4): e0006316, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29621234

RESUMO

BACKGROUND: Cysticercosis (CC) is a tissue infection caused by the larval cysts of the pork tapeworm Taenia solium. It is usually acquired by eating contaminated food or drinking water. CC Cysts can develop in the muscles, the eyes, the brain, and/or the spinal cord. T. solium is found worldwide, but its prevalence has decreased in developed countries due to stricter meat inspection and better hygiene and sanitation. Nevertheless, CC is still a leading cause of seizures and epilepsy. In Spain, The disease is not nationally reportable and data on CC infected animals are also missing, despite the European Directive 2003/99/EC. METHODOLOGY/PRINCIPAL FINDINGS: We performed a retrospective descriptive study using the Spanish Hospitalization Minimum Data Set (CMBD). Data with ICD-9 CM cysticercosis code ("123.1") placed in first or second diagnostic position from 1997 to 2014 were analyzed. Hospitalization rates were calculated and clinical characteristics were described. Spatial distribution of cases and their temporal behavior were also assessed. A total of 1,912 hospital discharges with clinical cysticercosis were identified. From 1998 to 2008, an increasing trend in the number of CC hospitalizations was observed, decreasing afterwards, in parallel with a decrease in the external migration rate. The Murcia region had the highest median hospitalization rate (13.37 hospitalizations/100,000 population), followed by Navarra and Madrid. The 16-44 age group was the most represented (63.6%). The three most frequent associated diagnoses were epilepsy and convulsions (49.5%), hydrocephalus (11.8%) and encephalitis/myelitis/meningitis (11.6%). CONCLUSIONS/SIGNIFICANCE: There is a need for a common strategy on data collection, monitoring and reporting, which would facilitate a more accurate picture on the CC epidemiological scenario. Even if most cases might be imported, improving the human and animal CC surveillance will result useful both in gaining extended disease knowledge and reducing morbidity and related-costs.


Assuntos
Cisticercose/epidemiologia , Alta do Paciente/tendências , Taenia solium/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Carne/parasitologia , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
6.
Rev. cuba. obstet. ginecol ; 37(4): 541-550, oct.-dic. 2011.
Artigo em Espanhol | LILACS | ID: lil-615238

RESUMO

Introducción: conocer los factores de riesgo y realizar el autoexamen de mama es de vital importancia para prevenir el cáncer de mama, una de las principales causas de muertes prevenibles en el sexo femenino. Objetivo: modificar el conocimiento sobre los factores de riesgo que causan el cáncer de mamas. Métodos: se realizó un estudio de intervención en el Local # 4 del Policlínico Comunitario Docente, Arturo Puig Ruiz de Villa, municipio Minas, en Camagüey el período comprendido entre enero de 2009 a junio de 2010. El universo quedó constituido por 219 féminas y la muestra fue de 119 según muestreo intencional puro no probabilístico, se confeccionó un cuestionario según bibliografía revisada e interés de los autores, con variables como edad, antecedentes familiares de cáncer, ingestión de tabletas anticonceptivas y hábitos tóxicos, frecuencia con que se realiza el autoexamen de mama. Los resultados fueron procesados mediante un paquete estadístico SPSS. Se aplicó la estadística descriptiva e inferencial con tablas. Resultados: predominó el grupo de edades, 40 - 49, 68 (57,14 por ciento), antecedentes familiares 71 (59,66 por ciento), contraceptivos hormonales usaron 92 (77,31 por ciento) antes de la intervención y después 5 (4,20 por ciento), con hábito tóxico 103 (86,55 por ciento) lo practicaban, después 5 (4,20 por ciento) mantuvieron el hábito, la práctica del autoexamen de mamas 68 (57,14 por ciento) lo realizan una vez al año, después de la intervención el 84,03 por ciento mensual. Conclusiones: se elevó el nivel de conocimiento que demuestra con este la utilidad de los estudios de intervención para disminuir factores de riesgo en la población


Introduction: breast carcinoma is the commonest cancer among women and the leading cause of death in the age-group 40-44. The knowledge of risk factors and the breast self- examination are essential for its prevention. Objective: to modify the knowledges on the risk factors leading to breast cancer. Methods: an interventional study was conducted in the Arturo Puig Ruiz de Villa Teaching Community Policlinic, Minas municipality, Camagüey province from January, 2009 to June, 2010. Universe included 210 women and sample included 119 according a non-probabilistic pure intentional sampling; a questionnaire was designed using the following variables: age, cancer family history, use of contraceptive tablets and toxic habits, as well as the frequency of breast self-examination. Results were processed by a SPSS statistic package. The descriptive and inferential statistics was applied using tables. Results: there was predominance of age-groups 40-69, 68 (57.14 percent), 71 family histories (59.66 percent), 92 used hormonal contraceptives (77.31 percent) before intervention and 5 after it (4.20 percent), 103 were smokers (86.55 percent), afterwards only 5 (4.20 percent) remains the habit, 68 patients practiced the breast self-examination (57.14 percent) carried out yearly, after intervention the 84.03 percent make it monthly. Conclusions: the knowledge increase demonstrating the usefulness of interventional studies to decrease the risk factors in population


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Autoexame de Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Impactos da Poluição na Saúde/prevenção & controle
7.
Invest Ophthalmol Vis Sci ; 49(6): 2506-11, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18296660

RESUMO

PURPOSE: To evaluate the possible correlation between the visual field defects in patients with primary open-angle glaucoma (POAG) and the expression and enzymatic activity of nitric oxide synthase (NOS) isoenzymes and nitrotyrosine in trabecular meshwork (TM) samples. METHODS: TM specimens were collected from 146 patients with POAG by using standard filtration surgery. Visual field defects were evaluated by perimetry. Expression of endothelial (e)NOS and inducible (i)NOS were evaluated by quantitative RT-PCR. Constitutive (Ca2+-dependent) and iNOS (Ca2+-independent) activities were measured by the conversion of L-[14C]-arginine to L-[14C]-citrulline. In four TM specimens from POAG-affected eyes and in three human donor control eyes, 3-nitrotyrosine was localized by immunohistochemistry. The marker of lipid peroxidation malondialdehyde (MDA) was measured by the thiobarbituric acid test in samples of aqueous humor (AH) from 48 patients with either POAG or cataracts. RESULTS: The results showed an upregulation of iNOS and a downregulation of calcium-dependent NOS correlated with visual field defects. Expression and activity of iNOS increased in parallel with visual field defects. However, constitutive activity decreased as the visual field defect increased. Nitrotyrosine was observed only in the cells of the TM specimens from eyes with severe POAG. CONCLUSIONS: The increased expression and activity of iNOS in the TM of patients with POAG are proportional to the visual field defect and could lead to the increased of nitrotyrosine levels which may serve as marker of oxidative stress in the progression of cell death of the TM in POAG.


Assuntos
Regulação Enzimológica da Expressão Gênica/fisiologia , Glaucoma de Ângulo Aberto/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo II/genética , Estresse Oxidativo/fisiologia , Malha Trabecular/metabolismo , Tirosina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Cálcio/farmacologia , Humanos , Pressão Intraocular , Peroxidação de Lipídeos , Malondialdeído/metabolismo , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirosina/metabolismo , Regulação para Cima , Transtornos da Visão/metabolismo , Testes de Campo Visual , Campos Visuais
8.
J Clin Microbiol ; 46(1): 385-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17977995

RESUMO

Blood samples and a bone biopsy specimen from one patient diagnosed with spondylodiscitis of unknown etiology were analyzed by quantitative real-time PCR to detect Brucella melitensis. The high sensitivity and specificity of this assay allowed the diagnosis of brucellar spondylitis within 24 h, a result that we were unable to obtain through the use of conventional methods.


Assuntos
Brucella melitensis/isolamento & purificação , Brucelose/diagnóstico , Reação em Cadeia da Polimerase/métodos , Espondilite/microbiologia , Idoso de 80 Anos ou mais , Sangue/microbiologia , Medula Óssea/microbiologia , Brucella melitensis/genética , Feminino , Humanos
9.
Hepatology ; 46(3): 813-22, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17654701

RESUMO

UNLABELLED: Caveolae participate in several cellular processes such as vesicular transport, cholesterol homeostasis, regulation of signal transduction, integrin signaling, and cell growth. The expression and functional role of caveolin (Cav), the most abundant protein of caveolae, has been reported in liver and in different hepatocyte cell lines, in human cirrhotic liver, and in hepatocellular carcinomas. The role of Cav-1 in liver regeneration after partial hepatectomy (PH) has been investigated as a model of liver proliferation in vivo. Our results show that Cav-1 increases in liver after PH with a redistribution of the protein from the caveola-enriched domain to the noncaveolar fraction. Moreover, the Cav-1 located in the noncaveolar fraction is phosphorylated in tyrosine 14, even though the Cav-1 gene is dispensable for liver regeneration after PH, as deduced from data obtained with commercially available animals lacking this gene. In addition to this, the proinflammatory stimulation of hepatocytes induces Cav-1 translocation to a noncaveolar fraction and tyrosine 14 phosphorylation mainly through the activation of tyrosine kinases such as Src. CONCLUSION: These results support a dynamic role for Cav-1 in liver proliferation both in vivo after PH and in vitro in cultured hepatic cell lines, but with minimal implications for the liver regeneration process.


Assuntos
Caveolina 1/metabolismo , Hepatócitos/metabolismo , Regeneração Hepática , Fígado/metabolismo , Animais , Proteína Tirosina Quinase CSK , Caveolina 1/análise , Caveolina 1/genética , Linhagem Celular , Citocinas/metabolismo , Hepatectomia , Hepatócitos/química , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/citologia , Regeneração Hepática/genética , Camundongos , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Tirosina/metabolismo , Quinases da Família src
10.
Hepatology ; 45(3): 631-8, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17326157

RESUMO

UNLABELLED: Cyclooxygenase-2 (COX-2) is upregulated in many cancers, and the prostanoids synthesized increase proliferation, improve angiogenesis, and inhibit apoptosis in several tissues. To explore the function of COX-2 in liver, transgenic (Tg) mice were generated containing a fusion gene (LIVhCOX-2) consisting of human COX-2 cDNA under the control of the human ApoE promoter. Six lines were developed; all of them expressed the LIVhCOX-2 transgene selectively in hepatocytes. The Tg mice exhibited a normal phenotype, and the increased levels of PGE2 found were due to the constitutively expressed COX-2. Histological analysis of different tissues and macroscopic examination of the liver showed no differences between wild-type (Wt) and Tg animals. However, Tg animals were resistant to Fas-mediated liver injury, as demonstrated by low levels of plasmatic aminotransferases, a lesser caspase-3 activation, and Bax levels and an increase in Bcl-2, Mcl-1, and xIAP proteins, when compared with the Wt animals. Moreover, the resistance to Fas-mediated apoptosis is suppressed in the presence of COX-2-selective inhibitors, which prevented prostaglandin accumulation in the liver of Tg mice. CONCLUSION: These results demonstrate that expression of COX-2-dependent prostaglandins exerted a protection against liver apoptosis.


Assuntos
Apoptose/fisiologia , Ciclo-Oxigenase 2/metabolismo , Hepatócitos/enzimologia , Fígado/patologia , Receptor fas/fisiologia , Alanina Transaminase/sangue , Animais , Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Caspases/metabolismo , Ciclo-Oxigenase 2/genética , Dinoprostona/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Fígado/enzimologia , Camundongos , Camundongos Transgênicos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Receptor fas/imunologia
11.
Biochem J ; 398(3): 371-80, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16800815

RESUMO

We have investigated the mechanism of COX-2 (cyclo-oxygenase 2)-dependent inhibition of apoptosis in liver, a key pathway underlying proliferative actions of COX-2 in liver cancers, cirrhosis, chronic hepatitis C infection and regeneration after partial hepatectomy. Stable expression of COX-2 in CHL (Chang liver) cells induced proliferation, with an increase in the proportion of cells in S-phase, but no other significant changes in cell-cycle distribution. This was associated with a marked inhibition of the apoptotic response to serum deprivation, an effect mimicked by treating empty-vector-transfected control cells (CHL-V cells) with prostaglandin E2 and prevented in COX-2-expressing cells (CHL-C cells) treated with selective inhibitors of COX-2. Serum-deprived CHL-V cells displayed several indicators of activation of intrinsic apoptosis: caspases 9 and 3 activated within 6 h and caspase 8 within 18 h, Bax expression was induced, cytochrome c was released to the cytosol, and PARP-1 [poly(ADP-ribose) polymerase 1] cleavage was evident in nuclei. COX-2 expression blocked these events, concomitant with reduced expression of p53 and promotion of Akt phosphorylation, the latter indicating activation of survival pathways. CHL cells were resistant to stimulation of the extrinsic pathway with anti-Fas antibody. Moreover, in vivo expression of GFP (green fluorescent protein)-labelled COX-2 in mice by hydrodynamics-based transient transfection conferred resistance to caspase 3 activation and apoptosis induced by stimulation of Fas.


Assuntos
Apoptose/fisiologia , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica , Hepatócitos/enzimologia , Biomarcadores/metabolismo , Linhagem Celular , Ciclo-Oxigenase 2/genética , Humanos , Fase S/fisiologia
12.
Carcinogenesis ; 26(4): 753-61, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15661807

RESUMO

The effect of the expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis on cell migration, the secretion of matrix metalloproteinases (MMPs) and the adhesion of human hepatoma cell lines has been investigated. A close correlation was observed between the expression of COX-2 under basal conditions and the secretion of MMP-2 and MMP-9. Cell migration in HuH-7 cells, which express high constitutive levels of COX-2 was significantly inhibited by selective inhibitors of COX-2 and enhanced by exogenous addition of PGE2. Hepatocellular carcinoma (HCC) cells expressed beta1 and alphaV beta3 integrins, exhibiting an increase in cell adhesion onto fibronectin and vitronectin. Moreover, addition of PGE2 increased the beta1 integrin levels and adhesion on vitronectin in HuH-7 cells. Inhibitors of MEK/ERK, p38 MAPK, protein kinases A and C impaired the migration of HuH-7 cells induced by PGE2, indicating the involvement of multiple pathways in the process. Taken together, these results support the existence of a relationship between COX-2-derived PGE2 synthesis, and migration and adhesion through an integrin-dependent pathway in HCC cells.


Assuntos
Carcinoma Hepatocelular/patologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Dinoprostona/farmacologia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ciclo-Oxigenase 2 , Humanos , Integrina alfaVbeta3/metabolismo , Integrinas/metabolismo , Neoplasias Hepáticas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Receptores de Vitronectina/metabolismo , Células Tumorais Cultivadas
13.
J Hepatol ; 40(6): 963-70, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15158337

RESUMO

BACKGROUND/AIMS: A regeneration process intended to restore organ function follows liver hepatotoxicity induced by a necrogenic dose of thioacetamide (TAM). METHODS: The expression of genes related to inflammation such as nitric oxide synthase-2 (NOS-2) and cyclooxygenase-2 (COX-2) has been analyzed in the course of the regenerative response, using NOS-2 KO mice or animals treated with selective inhibitors of COX-2. RESULTS: All animals lacking both activities survived to the hepatotoxic administration. However, animals deficient for NOS-2 exhibited more severe organ damage in view of the levels of hepatic serum markers of function, as well as an attenuated activation of NF-kappaB. The levels of C/EBPs were determined as markers of hepatocyte de-differentiation and regeneration, and the expression of COX-2 in TAM treated animals was concomitant with a decrease in C/EBP-alpha level. Analysis of cyclin D1, E and PCNA correlated with hepatocytes entering into the S phase of cell cycle by the effect of TAM. CONCLUSIONS: These data indicate that hepatocytes from TAM-treated mice express NOS-2 and COX-2 proteins and initiate the regeneration process that follows acute liver injury. However, the absence of NO delays hepatocyte regeneration, whereas COX-2-inhibition appears to decrease liver damage.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Hepatócitos/enzimologia , Regeneração Hepática/fisiologia , Prostaglandina-Endoperóxido Sintases/genética , Tioacetamida/farmacologia , Animais , Carcinógenos/farmacologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Deleção de Genes , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Regeneração Hepática/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Mol Pharmacol ; 63(3): 671-7, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12606776

RESUMO

The effect of rofecoxib, a selective cyclooxygenase-2 inhibitor, on inflammatory signaling has been investigated in elicited murine peritoneal macrophages. Macrophages treated with 10 microM rofecoxib exhibited an important inhibition in the early activation of nuclear factor kappa B (NF-kappa B) and the mitogen-activated protein kinase p38, the extracellular-regulated kinase p44, and the c-Jun N-terminal kinase. Moreover, this drug decreased the protein levels of nitric-oxide synthase-2 and cyclooxygenase-2 in lipopolysaccharide (LPS)-treated macrophages. Rofecoxib delayed and attenuated NF-kappa B activation, which impaired significantly the expression of kappa B-dependent genes. This drug and related coxibs did not affect cell viability and protected against LPS-induced apoptosis through the impairment of the inflammatory response. These data show an additional anti-inflammatory mechanism of selective cyclooxygenase-2 inhibitors through the attenuation of macrophage activation.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Isoenzimas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , NF-kappa B/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Linhagem Celular , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Ativação Enzimática , Expressão Gênica/efeitos dos fármacos , Quinase I-kappa B , Lactonas/farmacologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Proteínas Serina-Treonina Quinases/metabolismo , Sulfonas
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