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1.
Rev. Ciênc. Méd. Biol. (Impr.) ; 19(1): 78-84, jun 17, 2020. fig
Artigo em Português | LILACS | ID: biblio-1358763

RESUMO

Objetivo: este estudo teve como objetivo traçar o perfil sociodemográfico e epidemiológico de pacientes com AIDS residentes microrregião na região de saúde que compreende o município de Alagoinhas ­ BA, no período de 2007-2017. Metodologia: trata-se de um estudo epidemiológico descritivo, exploratório de fonte secundária de dados. As variáveis investigadas foram: gênero, faixa etária, grau de escolaridade, município de residência, cor, categoria de exposição e evolução do caso. Resultados: durante o período 2007 ­ 2017 constataram-se 459 casos registrados no SINAN, de AIDS em adultos na Região de Saúde do município. Assim, verificou-se em adulto uma tendência de crescimento no número de casos na microrregião de Alagoinhas, acentuado no ano de 2014 (95 casos), e com considerável aumento constatado no ano de 2017 (90 casos). Evidenciou-se que 227 pacientes pertenciam ao sexo masculino e 232 ao sexo feminino, havendo predomínio de casos, todavia, na faixa etária entre 20 a 34 anos. Houve maior número de casos em adultos, faixa etária de 20-34 e 35-49, e dentre estes, o número de casos foi maior em indivíduos que têm relação heterossexual, seguido de indivíduos que têm relação homossexual; houve alto número de casos em indivíduos que possuem relações sexuais só com homens, totalizando 258, seguido de só com mulheres (135). Conclusão: o presente estudo permitiu compreender que os indivíduos adultos vivendo com HIV/AIDS, no período de 2007 a 2017, seguem a tendência nacional, contudo a melhoria do acesso aos serviços, qualidade da atenção, proporciona uma maior qualidade de vida aos pacientes.


Objective: this study aimed to outline the sociodemographic and epidemiological profile of AIDS patients living in ­ the health region of the Health Region comprising the municipality of Alagoinhas ­ BA, in the period 2007-2017. Methodology: this is a descriptive, exploratory epidemiological study of a secondary source of data. The variables investigated were: gender, age group, education level, municipality of residence, color, category of exposure and evolution of the case. Results: during the period 2007-2017, 459 cases were recorded in the SINAN of AIDS in adults in the Health Region of the municipality. Thus, in adults, there was a trend of growth in the number of cases in the Alagoinhas microregion, accentuated in 2014 (95 cases), and with a considerable increase observed in 2017 (90 cases), it was evidenced that 227 patients belonged were male, and 232 were female, with cases predominating, however, in the age group between 20 and 34 years. There were more cases in adults, age range 20-34 and 35-49, and among these, the number of cases was higher in individuals who have a heterosexual relationship, followed by individuals who have a homosexual relationship, there were a high number of cases in individuals who have sex with men alone, totaling 258, followed by only with women (135). Conclusion: the present study made it possible to understand that adult individuals living with HIV / AIDS, from 2007 to 2017, follow the national trend, however, improving access to services and quality of care provides a better quality of life for patients


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Epidemiologia , HIV , Escolaridade , Identidade de Gênero , Grupos Etários , Estudos Epidemiológicos , Epidemiologia Descritiva , Base de Dados , Estudos de Avaliação como Assunto
2.
Cell Commun Signal ; 17(1): 106, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443721

RESUMO

BACKGROUND: HER3/ErbB3 receptor deletion or blockade leads to tumor cell apoptosis, whereas its overexpression confers anti-cancer drug resistance through upregulation of protective mechanisms against apoptosis. We produced the anti-HER3 antibody 9F7-F11 that promotes HER3 ubiquitination and degradation via JNK1/2-dependent activation of the E3 ubiquitin ligase ITCH, and that induces apoptosis of cancer cells. Cellular FLICE-like inhibitory protein (c-FLIP) is a key regulator of apoptotic pathways. Here, we wanted to determine the mechanisms underlying the pro-apoptotic effect of 9F7-F11. METHODS: Anti-HER3 antibody-induced apoptosis was assessed by western blot, and by flow cytometry measurement of Annexin V/7-AAD-labelled tumor cells (BxPC3, MDA-MB-468 and DU145 cell lines). c-FLIP/ITCH interaction and subsequent degradation/ubiquitination were investigated by co-immunoprecipitation of ITCH-silenced vs scramble control cells. The relationship between ITCH-mediated c-FLIP degradation and antibody-induced apoptosis was examined by western blot and flow cytometry of tumor cells, after ITCH RNA interference or by pre-treatment with ITCH chemical inhibitor chlorimipramine (CI). RESULTS: Following incubation with 9F7-F11, cancer cell apoptosis occurs through activation of caspase-8, - 9 and - 3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP). Moreover we showed that ubiquitination and proteasomal degradation of the anti-apoptotic protein c-FLIP was mediated by USP8-regulated ITCH recruitment. This effect was abrogated by ITCH- and USP8-specific RNA interference (siRNA), or by the ITCH chemical inhibitor CI. Specifically, ITCH silencing or CI blocked 9F7-F11-induced caspase-8-mediated apoptosis of tumor cells, and restored c-FLIP expression. ITCH-silencing or CI concomitantly abrogated HER3-specific antibody-induced apoptosis of Annexin V/7-AAD-labelled BxPC3 cells. 9F7-F11 favored the extrinsic apoptosis pathway by inducing TRAIL-R2/DR5 upregulation and TRAIL expression that promoted the formation of death-inducing signaling complex (DISC), leading to caspase-8-mediated apoptosis. Incubation with 9F7-F11 also induced BID cleavage, BAX upregulation and BIM expression, which initiated the caspase-9/3-mediated mitochondrial death pathway. The anti-HER3 antibody pro-apoptotic effect occurred concomitantly with downregulation of the pro-survival proteins c-IAP2 and XIAP. CONCLUSIONS: The allosteric non-neuregulin competing modulator 9F7-F11, sensitizes tumor cells to DR5/caspase-8-mediated apoptosis through ITCH-dependent downregulation of c-FLIP.


Assuntos
Anticorpos Monoclonais Murinos/metabolismo , Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Caspase 8/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de Sinais
3.
J Environ Manage ; 246: 617-624, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207500

RESUMO

Degradation of petroleum hydrocarbons using bacterial consortia may be a means of optimizing bioremediation techniques. In this study, bacterial strains were isolated from the digestive tract of polychaete worms and evaluated concerning the potential of the bacteria to degrade petroleum compounds (Acinetobacter sp., Bacillus sp., Pantoea sp. and Enterobacter sp.). The strains were separately screened regarding their potential to degrade oil after 24 h. The main experiment was carried out for 30 days with the addition of nitrogen, phosphorus and potassium (NPK) after 15 days (Bact-NPK15) and 28 days (Bact-NPK28) and without NPK (Bact). The Bact treatment biomass remained stable until the 20th day of the experiment. C13-C40 n-alkanes were degraded with all treatments in the following order: Bact>Bact-NPK28>Bact-NPK15. Significant differences were observed between the controls and all treatments (p = 0.00031). Measurement of polycyclic aromatic hydrocarbons (PAHs) indicates a lower contribution of these compounds in the Bact-NPK28 treatment, although no significant difference between groups was observed. Bact-NPK28 was able to remove 40% of naphthalene, while Bact-NPK15 removed 20%; this effect was not observed in Bact. Higher hopane degradation levels were observed in Bact and, to a lesser extent, in Bact-NPK28. NPK application for 28 days mainly favored PAH degradation. The evaluated consortium thus exhibits potential in the bioremediation of petroleum-contaminated areas.


Assuntos
Anelídeos , Petróleo , Poliquetos , Hidrocarbonetos Policíclicos Aromáticos , Animais , Bactérias , Biodegradação Ambiental , Suplementos Nutricionais , Fertilizantes
4.
3 Biotech ; 9(4): 155, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30944802

RESUMO

In this study, Rhizophora mangle L. mangrove plants and plant growth-promoting bacteria were evaluated for their ability to degrade polycyclic aromatic hydrocarbons in diesel oil-contaminated sediment. The diesel-contaminated soil was sown with plant growth-promoting bacteria in the R. mangle L. rhizosphere and monitored for 120 days in a greenhouse. The plant growth-promoting bacteria Pseudomonas aeruginosa and Bacillus sp. were analyzed for their ability to degrade eight priority polycyclic aromatic hydrocarbons, achieving a removal rate for naphthalene (80%), acenaphthene (> 60%), anthracene (> 50%), benzo(a)anthracene (> 60%), benzo(a)pyrene (> 50%) and dibenzo(a,h)anthracene (> 90%) in the treatments with and without plants. R. mangle L. demonstrated a removal rate above 50% for acenaphthene and fluoranthene. The bacterial strains promoted the development of the plant propagule in 55% of sediment contaminated with diesel. Scanning electron microscopy revealed the formation of biofilms by the strains in the roots of the plants in contact with the diesel. Thus, the interaction between Rhizophora mangle L. and the bacterial strains (Bacillus sp. and P. aeruginosa) demonstrated the potential of the strains to degrade diesel and bioremediate mangroves impacted by diesel oil.

5.
São Luís; s.n; 2019. 12 p. ilus. (RESMULT-01).
Não convencional em Português | CONASS, Coleciona SUS, SES-MA | ID: biblio-1118067

RESUMO

Esta cartilha é destinada aos usuários que se submeteram a intervençõescirúrgicasinternados nas Unidades de Terapia Intensiva do Hospital de Alta Complexidade Dr. Carlos Macieira, São Luís/MA. O objetivo é repassar de forma clara e objetiva informações simples e seguras sobre os cuidados no pós-operatório durante seu processo de reabilitaçãoem domicílio.Este informativo foi construído num coletivo composto por profissionais das áreas de enfermagem, nutrição, odontologia e fisioterapia do Programa de Residência Multiprofissional em Terapia Intensiva da Secretaria de Estado do Maranhãocomapoio da Empresa Maranhense de Serviços hospitalares (EMSERH).


Assuntos
Humanos , Alta do Paciente , Terapêutica/enfermagem , Educação de Pacientes como Assunto
6.
Urol Int ; 100(4): 476-484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719304

RESUMO

BACKGROUND: The activation of Fas/Fas ligand (FasL) and DR4-DR5/tumor necrosis factor-related-apoptosis-inducing ligand (TRAIL) pathways in cancer cells triggers apoptosis. The objective of this study was to investigate the prognostic value of soluble FasL (sFasL) and soluble (sTRAIL) in the serum of patients with bladder cancer. METHODS: The sFasL and sTRAIL levels in the sera of patients with bladder cancer or healthy donors were determined using the enzyme-linked immunosorbent assay. Micro-culture tetrazolium viability assay and Western blot were used to analyze cell cytotoxicity and death receptors protein expression respectively. RESULTS: Whether no difference in sTRAIL levels was seen between patients and controls, the level of sFasL was higher in patients than that in healthy donors. According to, sFasL level was the highest in the serum of patients with superficial stage or low- and medium-grade cancer. Moreover, sFasL in patients with superficial noninvasive bladder tumors or low- and medium-grade cancers was higher than that in patients with invasive carcinomas and high-grade cancers. Patients with high levels of sFasL survive longer than those with low levels, probably related to the cytotoxic potential of FasL preserved in its soluble form. CONCLUSION: The data suggest that monitoring the level of sFasL and its cytotoxic activity could be a prognostic marker in the follow-up of patients with bladder cancer.


Assuntos
Carcinoma de Células de Transição/sangue , Proteína Ligante Fas/sangue , Ligante Indutor de Apoptose Relacionado a TNF/sangue , Neoplasias da Bexiga Urinária/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Tunísia , Bexiga Urinária/patologia
7.
Tumour Biol ; 37(6): 7873-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26700664

RESUMO

Various studies in western countries found Akt amplification to be a frequent event in human cancers, including bladder, but the correlation with clinicopathological features is controversial. Such studies have not been reported in African populations, including Tunisians. The purpose of this study was to assess expression of the phosphorylated/activated forms of Akt in tumors from Tunisian patients with bladder cancer and to correlate its expression with pathological and clinical parameters of the disease. The study included 72 patients of whom 34 were diagnosed as low- to medium-grade and 35 as high-grade; 30 were muscle stage and 39 non-muscle stage. Primary tumors from these patients, normal adjacent tissues, or bladder cancer cell-lines were analyzed for Ser473 phosphorylated Akt expression by Western blot. Seventy-two percent of primary tumors from patients with bladder cancer had increased levels of p-Akt. The p-Akt levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer. In invasive carcinoma, the p-Akt level was significantly higher than in superficial non-invasive bladder tumors. Concerning the influence of tobacco on Akt activation, no significant differences of p-Akt expression were found between non-smoker and smoker patients. Altogether, our results suggest that Akt activation can provide useful prognostic information and that tobacco represents a serious risk factor for recurrence in a cohort of Tunisian patients.


Assuntos
Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , População Negra/etnologia , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosforilação , Prognóstico , Tunísia/epidemiologia , Neoplasias da Bexiga Urinária/etnologia , Neoplasias da Bexiga Urinária/patologia
8.
J Med Chem ; 58(11): 4521-8, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-25973667

RESUMO

Gold phosphine complexes, such as auranofin, have been recognized for decades as antirheumatic agents. Clinical trials are now underway to validate their use in anticancer or anti-HIV treatments. However, their mechanisms of action remain unclear. A challenging question is whether the gold phosphine complex is a prodrug that is administered in an inactive precursor form or rather that the gold atom remains attached to the phosphine ligand during treatment. In this study, we present two novel gold complexes, which we compared to auranofin and to their phosphonium analogue. The chosen ligand is a phosphine-based smart probe, whose strong fluorescence depends on the presence of the gold atom. The in vitro biological action of the gold complexes and the phosphonium derivative were investigated, and a preliminary in vivo study in healthy zebrafish larvae allowed us to evaluate gold complex biodistribution and toxicity. The different analyses carried out showed that these gold complexes were stable and behaved differently from phosphonium and auranofin, both in vitro and in vivo. Two-photon microscopy experiments demonstrated that the cellular targets of these gold complexes are not the same as those of the phosphonium analogue. Moreover, despite similar IC50 values in some cancer cell lines, gold complexes displayed a low toxicity in vivo, in contrast to the phosphonium salt. They are therefore suitable for future in vivo investigations.


Assuntos
Antineoplásicos/farmacologia , Auranofina/farmacologia , Proliferação de Células/efeitos dos fármacos , Ouro/química , Larva/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Fosfinas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antirreumáticos/química , Antirreumáticos/farmacocinética , Antirreumáticos/farmacologia , Auranofina/química , Humanos , Larva/crescimento & desenvolvimento , Ligantes , Modelos Moleculares , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade , Distribuição Tecidual , Células Tumorais Cultivadas , Peixe-Zebra/crescimento & desenvolvimento
9.
Retrovirology ; 10: 75, 2013 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-23880157

RESUMO

BACKGROUND: Transformation by the Tax oncoprotein of the human T cell leukemia virus type 1 (HTLV-1) is governed by actions on cellular regulatory signals, including modulation of specific cellular gene expression via activation of signaling pathways, acceleration of cell cycle progression via stimulation of cyclin-dependent kinase activity leading to retinoblastoma protein (pRb) hyperphosphorylation and perturbation of survival signals. These actions control early steps in T cell transformation and development of Adult T cell leukemia (ATL), an aggressive malignancy of HTLV-1 infected T lymphocytes. Post-translational modifications of Tax by phosphorylation, ubiquitination, sumoylation and acetylation have been implicated in Tax-mediated activation of the NF-κB pathway, a key function associated with Tax transforming potential. RESULTS: In this study, we demonstrate that acetylation at lysine K(346) in the carboxy-terminal domain of Tax is modulated in the Tax nuclear bodies by the acetyltransferase p300 and the deacetylases HDAC5/7 and controls phosphorylation of the tumor suppressor pRb by Tax-cyclin D3-CDK4-p21(CIP) complexes. This property correlates with the inability of the acetylation deficient K(346)R mutant, but not the acetylation mimetic K(346)Q mutant, to promote anchorage-independent growth of Rat-1 fibroblasts. By contrast, acetylation at lysine K(346) had no effects on the ability of Tax carboxy-terminal PDZ-binding domain to interact with the tumor suppressor hDLG. CONCLUSIONS: The identification of the acetyltransferase p300 and the deacetylase HDAC7 as enzymes modulating Tax acetylation points to new therapeutic targets for the treatment of HTLV-1 infected patients at risk of developing ATL.


Assuntos
Transformação Celular Viral , Produtos do Gene tax/metabolismo , Histona Desacetilases/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Lisina/metabolismo , Processamento de Proteína Pós-Traducional , Fatores de Transcrição de p300-CBP/metabolismo , Acetilação , Animais , Linhagem Celular , Fibroblastos/virologia , Humanos , Ratos
10.
Retrovirology ; 9: 102, 2012 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-23217160

RESUMO

BACKGROUND: Retroviruses HTLV-1 and HTLV-2 have homologous genomic structures but differ significantly in pathogenicity. HTLV-1 is associated with Adult T cell Leukemia (ATL), whereas infection by HTLV-2 has no association with neoplasia. Transformation of T lymphocytes by HTLV-1 is linked to the capacity of its oncoprotein Tax-1 to alter cell survival and cell cycle control mechanisms. Among these functions, Tax-1-mediated activation of cellular gene expression via the NF-κB pathway depends on Tax-1 post-translational modifications by ubiquitination and sumoylation. The Tax-2 protein of HTLV-2B (Tax-2B) is also modified by ubiquitination and sumoylation and activates the NF-κB pathway to a level similar to that of Tax-1. The present study aims to understand whether ubiquitination and sumoylation modifications are involved in Tax-2B-mediated activation of the NF-κB pathway. RESULTS: The comparison of Tax-1 and Tax-2B lysine to arginine substitution mutants revealed conserved patterns and levels of ubiquitination with notable difference in the lysine usage for sumoylation. Neither Tax-1 nor Tax-2B ubiquitination and sumoylation deficient mutants could activate the NF-κB pathway and fusion of ubiquitin or SUMO-1 to the C-terminus of the ubiquitination and sumoylation deficient Tax-2B mutant strikingly restored transcriptional activity. In addition, ubiquitinated forms of Tax-2B colocalized with RelA and IKKγ in prominent cytoplasmic structures associated with the Golgi apparatus, whereas colocalization of Tax-2B with the RelA subunit of NF-κB and the transcriptional coactivator p300 in punctate nuclear structures was dependent on Tax-2B sumoylation, as previously observed for Tax-1. CONCLUSIONS: Both Tax-1 and Tax-2 activate the NF-κB pathway via similar mechanisms involving ubiquitination and sumoylation. Therefore, the different transforming potential of HTLV-1 and HTLV-2 is unlikely to be related to different modes of activation of the canonical NF-κB pathway.


Assuntos
Produtos do Gene tax/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Vírus Linfotrópico T Tipo 2 Humano/fisiologia , NF-kappa B/metabolismo , Sumoilação , Sequência de Aminoácidos , Substituição de Aminoácidos , Núcleo Celular/metabolismo , Sequência Conservada , Proteína p300 Associada a E1A/metabolismo , Células HEK293 , Células HeLa , Interações Hospedeiro-Patógeno , Humanos , Quinase I-kappa B/metabolismo , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Transporte Proteico , Ativação Transcricional , Ubiquitinação
11.
Virology ; 408(1): 39-48, 2010 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-20875659

RESUMO

HTLV-1 is more pathogenic than HTLV-2 despite having a similar genome and closely related transactivating oncoproteins. Both Tax-1 protein from HTLV-1 and Tax-2 from HTLV-2 activate the NF-κB pathway. The mechanisms involved in Tax-1 deregulation of this signalling pathway have been thoroughly investigated, but little is known about regulation by Tax-2. We have compared the interaction of Tax-1 and Tax-2 with two key NF-κB signalling factors: TAK1-binding protein 2 (TAB2), an adaptor involved in the activation of TAK1 kinase, and RelA, the active subunit of the canonical RelA/p50 NF-κB transcription factor. Tax-2 formed stable complexes with both RelA and TAB2. These two NF-κB factors colocalized with Tax proteins in dotted cytoplasmic structures targeted by calreticulin, a multi-process calcium-buffering chaperone. Co-expression of RelA and/or TAB2 markedly increased Tax-mediated NF-κB activation. These findings provide new insights into the role of RelA, TAB2 and Tax in the deregulation of the NF-κB pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Calreticulina/análise , Estruturas Citoplasmáticas/virologia , Produtos do Gene tax/metabolismo , NF-kappa B/imunologia , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Cricetulus , Estruturas Citoplasmáticas/química , Produtos do Gene tax/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Vírus Linfotrópico T Tipo 2 Humano/imunologia , Humanos , NF-kappa B/metabolismo , Ligação Proteica
12.
Mol Cell Biol ; 28(2): 587-600, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18025104

RESUMO

Phosphoinositide 3-kinase (PI3K) participates in extracellular signal-regulated kinase 1 and 2 (ERK1-2) activation according to signal strength, through unknown mechanisms. We report herein that Gab1/Shp2 constitutes a PI3K-dependent checkpoint of ERK1-2 activation regulated according to signal intensity. Indeed, by up- and down-regulation of signal strength in different cell lines and through different methods, we observed that Gab1/Shp2 and Ras/ERK1-2 in concert become independent of PI3K upon strong epidermal growth factor receptor (EGFR) stimulation and dependent on PI3K upon limited EGFR activation. Using Gab1 mutants, we observed that this conditional role of PI3K is dictated by the EGFR capability of recruiting Gab1 through Grb2 or through the PI3K lipid product PIP(3), according to a high or weak level of receptor stimulation, respectively. In agreement, Grb2 siRNA generates, in cells with maximal EGFR stimulation, a strong dependence on PI3K for both Gab1/Shp2 and ERK1-2 activation. Therefore, Ras/ERK1-2 depends on PI3K only when PIP(3) is required to recruit Gab1/Shp2, which occurs only under weak EGFR mobilization. Finally, we show that, in glioblastoma cells displaying residual EGFR activation, this compensatory mechanism becomes necessary to efficiently activate ERK1-2, which could probably contribute to tumor resistance to EGFR inhibitors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Receptores ErbB/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Proteínas ras/metabolismo , Motivos de Aminoácidos , Animais , Linhagem Celular , Chlorocebus aethiops , Ativação Enzimática/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Proteína Adaptadora GRB2/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos
13.
Int J Hyg Environ Health ; 210(3-4): 447-54, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17347042

RESUMO

As part of environmental health surveillance programs related to solid waste incinerators located near Lisbon and on Madeira Island, human biomonitoring projects have been implemented in Portugal, some of them focused on cross-sectional surveys of heavy metals in blood. One of the general aims of these programs is to provide Portuguese data on the extent and pattern of human exposure to the pollutants potentially released in the stack gases from the incinerators, namely heavy metals. The present investigation reports information specifically on blood lead levels of newborn-mother pairs living in the vicinity of the incinerators under study, as well as of statistically similar participants living outside the exposed area. For Lisbon, lead levels determined at the baseline period (T0), as well as three subsequent evaluations of potential specific impacts of the incinerator (T1, T2 and T3) are described in order to investigate spatial and temporal trends of human exposure to lead. Available data for Madeira, namely lead levels in blood from the study population before the incinerator started operation, is also described. For Lisbon, analyses showed a statistically significant decrease of lead concentrations in maternal (p<0.001) and umbilical cord blood (p<0.001) during the whole monitoring period. Practically "overt" transplacental exposure to lead was observed only in the Lisbon biomonitoring project and for some cross-sectional surveys. Baseline levels for Madeira were the lowest found in all observations already performed in both programs (maternal and umbilical cord mean lead levels of 0.4 microg/dl and 0.3 microg/dl, respectively). No statistical associations have been found between lead levels in blood and age neither for global populations from Lisbon and Madeira nor for specific groups included in the different observational periods.


Assuntos
Poluentes Atmosféricos/sangue , Monitoramento Ambiental/métodos , Sangue Fetal/química , Incineração , Chumbo/sangue , Troca Materno-Fetal , Eliminação de Resíduos/métodos , Adolescente , Adulto , Estudos de Coortes , Monitoramento Epidemiológico , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Vigilância da População , Portugal/epidemiologia , Gravidez
14.
Int J Hyg Environ Health ; 210(3-4): 455-9, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17336151

RESUMO

As a part of environmental health surveillance programs related to Portuguese solid waste incinerators (SWI), two biomonitoring projects have been established to investigate additional exposure to lead in children under the age of 6 years living in the vicinity of those facilities. The above-mentioned programs, being the only ones in the country that integrate systematic observations on human exposure to heavy metals, have to provide systematic data from Portuguese regions on the extent and pattern of human exposure to heavy metals, namely to lead. The present paper is the third of a series of papers prepared to accomplish that objective in regards to lead exposure as evaluated by measuring lead levels in children under the age of 6 years. Altogether, 250 children from Lisbon and 247 from Madeira Island have already been involved in the investigation. The present study evaluates spatial and temporal trends of lead exposure, based on comparisons of children's blood lead levels, either stratified by living area (exposed and control groups), or by time of exposure (T0, the baseline time, and T1, after approximately 2 years of regular operation of the facilities). The results obtained correspond to a relatively reduced number of individuals. Possibly for this reason, they are not fully conclusive in relation to whether living in the vicinity of SWI represents an additional risk of higher exposure to lead. Time trends of lead exposure as evaluated by blood lead levels in children also do not show any clear pattern. These conclusions and the fact that altogether around 3% of children from the whole group have blood lead levels >or=10 microg/dl warrant further investigation in order to clarify the contribution of incinerator emissions to the levels of lead in children and to identify alternative sources for preventive purposes, taking into consideration the relevance of even low lead exposure from a public health perspective, mainly in relation to children.


Assuntos
Poluentes Atmosféricos/sangue , Exposição Ambiental/análise , Monitoramento Ambiental/métodos , Chumbo/sangue , Eliminação de Resíduos/métodos , Pré-Escolar , Estudos de Coortes , Monitoramento Epidemiológico , Feminino , Cabelo/química , Humanos , Incineração , Lactente , Chumbo/análise , Masculino , Vigilância da População , Portugal/epidemiologia
15.
Int J Hyg Environ Health ; 210(3-4): 439-46, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17324622

RESUMO

Human exposure to heavy metals makes it necessary to monitor these elements in the human body if the objective is to relate heavy metal exposure to adverse health effects. In Portugal, biomonitoring projects on heavy metals are being carried out on people living in the vicinity of solid waste incinerators. The projects are being developed in the ambit of two environmental health surveillance programs related to solid waste incineration facilities, one near Lisbon and the other on Madeira Island, that have the main objective of guaranteeing the safeguard of public health in relation to the potential negative impact of incineration processes on human health. These programs are the only ones in the country that integrate a systematic observation of human exposure to heavy metals as determined by the respective body burden in several population groups. Therefore, they are the only ones that are currently able to provide systematic data from Portuguese regions on the extent and pattern of human exposure to this type of pollutants. The present paper is the first of a series of three prepared papers with the objective of presenting and discussing available data. It addresses exposure to lead, cadmium and mercury as determined by their levels in blood of general population adults. Results suggest the effectiveness of source control measures in relation to both incinerators under study, similarly to what has been concluded from previous studies addressing exposure to dioxins. They also show, in relation to the baseline situation, a general significant trend for reduction of exposure to all studied heavy metals. Individuals from Lisbon seem to have a significantly higher body burden of the studied metals than those living in Madeira and, in general, metal exposure in men is significantly higher than in women, with the most relevant exception being the case of higher mercury levels in women, at the baseline and for both communities. Compared with published reference values for similar conditions, blood levels of cadmium, lead, and mercury of the present investigation seem to be relatively higher, in median terms and for extreme values, mainly in the case of cadmium and mercury. In the case of lead the differences are not so marked.


Assuntos
Poluentes Atmosféricos/sangue , Monitoramento Ambiental/métodos , Incineração , Metais Pesados/sangue , Eliminação de Resíduos/métodos , Adolescente , Adulto , Idoso , Estudos de Coortes , Monitoramento Epidemiológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Portugal/epidemiologia
16.
Chemosphere ; 67(9): S224-30, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17240423

RESUMO

Biomonitoring of dioxin body burden, as evaluated by PCDD/F levels in blood, has been carried out in a total of 138 adults from general population living in the vicinity of solid waste incinerators in Portugal. Measurements were performed included in cross-sectional surveys within two Environmental Health Surveillance Programs launched in response to ecotoxicological concern in relation to solid waste incinerators near Lisbon and in Madeira Island. Overall conclusion from first published results is indicative that dioxin exposure of global populations cannot be related to the emissions of these facilities, meaning that dioxin sources control seems to be effective in relation to both incinerators. Main objective of present work was to investigate potential determinants of dioxin levels in the studied populations. Findings from this investigation also suggest that incineration does not impact on dioxin blood levels of nearby residents. Follow-up of a small group of individuals (22) from Lisbon gives preliminary indication on temporal control effectiveness of the Lisbon facility. Regarding comparison between PCDD/F levels from Lisbon and Madeira communities, individuals from Lisbon show higher median PCDD/F levels, likely to be better explained by more highly polluted areas in Lisbon than by eventual differences in dietary habits of the studied groups. In fact, analysis performed on the diet of both groups (not detailed in the present study) does not show a statistically significant difference in relation to any of the most relevant foodstuffs in the context of dioxin exposure. Comparison between Lisbon and Madeira in relation to pattern of the single congeners for PCDD/Fs shows a very similar profile. The highest contributions to the PCDD/Fs toxicity came from 12378-PCDD, 23478-PCDF, Hexa-CDD, 2378-TCDD and Hexa-CDF.


Assuntos
Dioxinas/sangue , Exposição Ambiental , Poluentes Ambientais/sangue , Furanos/sangue , Incineração , Vigilância da População , Eliminação de Resíduos , Adulto , Benzofuranos/sangue , Saúde Ambiental , Feminino , Geografia , Humanos , Masculino , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/sangue , Portugal/epidemiologia
17.
Chemosphere ; 67(9): S231-7, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17215018

RESUMO

In the context of two Environmental Health Surveillance Programs, launched in response to public and scientific concern in relation to waste incinerators located near Lisbon and in Madeira Island, two human biomonitoring projects have been started in Portugal, focussed in dioxins and dioxin-like compounds in human milk. Results from the undertaken studies have already provided data on the extent and pattern of dioxin body burden of both studied groups as well as a preliminary temporal trend of dioxin levels for the population residing near Lisbon incinerator. The present paper investigates difference between exposed and non-exposed subjects under study and, from a preventive perspective, possible covariates of the dioxin levels in human milk. Emissions from both incinerators appear to be well controlled as there is no increase of human body burden of dioxins as measured in human milk of individuals living near these facilities. Concerning other determinants of dioxin levels, results suggest confirmation of previously found significant age-dependent trend towards higher levels of dioxins in aged subjects. On the contrary, association between mother's levels of dioxins and parity lost significance. Apart from the issue of incineration, the general conclusion for the general population is that living in Lisbon as compared to Madeira results in higher milk dioxin levels and possible health risks. The profile of the single congeners for PCDD/Fs in human milk from Madeira and Lisbon shows similar contributions for 12378-PCDD, 23478-PCDF, 123678-HCDD and 2378-TCDD, that account altogether for about 84% of the total identified dioxin body burden in the studied groups.


Assuntos
Benzofuranos/análise , Poluentes Ambientais , Habitação , Incineração , Leite Humano/química , Dibenzodioxinas Policloradas/análogos & derivados , Eliminação de Resíduos , Adulto , Benzofuranos/metabolismo , Benzofuranos/toxicidade , Monitoramento Ambiental , Poluentes Ambientais/análise , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Feminino , Geografia , Humanos , Dibenzodioxinas Policloradas/análise , Dibenzodioxinas Policloradas/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Vigilância da População , Portugal
18.
Rev. Dep. Psicol., UFF ; 12(2/3): 69-77, maio-dez. 2000. tab
Artigo em Português | Index Psicologia - Periódicos | ID: psi-37119

RESUMO

A atividade lúdica é identificada como fundamental para o desenvolvimento infantil, pois permite à criança integrar várias dimensões de sua identidade, assimilar a realidade e vivenciar papéis. Objetivou-se analisar a construção dos papéis de gênero através da situação de idade, quatro meninos e quatro meninas, e suas respectivas mães, agrupados conforme residissem em casas ou apartamentos. As entrevistas realizadas com as mães foram baseadas em roteiro especialmente elaborado, incluindo alguns itens do inventário HOME. Meninos e meninas tiveram como brinquedos/brincadeiras preferidos aqueles normalmente considerados apropriados para o seu gênero. As meninas apresentaram maior flexibilidade em relação à escolha de brinquedos/brincadeiras considerados do gênero oposto e os meninos apresentaram maior liberdade para brincar no ambiente externo. Não houve diferenciação entre estes em relação ao horário ou companhia para brincar. Comparando-se atividades lúdicas de mães e filhos, verificou-se que as primeiras brincavam mais de brincadeiras e fabricavam seus próprios brinquedos, e os últimos brincam mais com brinquedos, sendo estes industrializados. As mães das meninas estimulam mais o uso de brincadeiras e a fabricação de brinquedos do que as mães dos meninos. A qualidade do ambiente doméstico não apresentou variação. A construção dos papéis de gênero se dá simbolicamente através das atividades lúdicas e pelas contingências que envolvem a situação do brinquedo, como a estimulação por parte de suas mães em relação à forma de brincar e restrições em relação ao ambiente do brinquedo.(AU)


The act of playing has been identified as essential on child development, because it let children to integrate many different dimensions of their identity, assimilate reality, and experiment roles. This research intends to understand how do the construction of children’s roles of gender takes place through the act of playing. Eight children, four males and four females, from similar social classes, at the ages of 3 to 6 years old, and their mothers, were interviewed, stratified by living in houses or apartments. The interviews with the mothers were base on a program specially performed, including some items from HOME inventory. The favorite toys/children’s plays for boys and girls were those which are commonly considered appropriated for their gender. The girls were pliable on choosing the toys/children’s play considered appropriated for the other gender whereas the boys were more free top play outside. There were no differences on time spent or at the people the children chose to play with. It was observed that the mothers used to play with toys/children’s plays which were made and created by themselves, whereas their kids use to play with industrialized toys. The girl’s mothers stimulated more the children’s plays and the hands-made toys than boy’s mothers. The domestic environment’s quality didn’t show varieties. The construction of children’s roles of gender takes place through children’s plays and through the contingencies which involve the toy’s children situation, such as the stimulation from their mothers on how to play, and restrictions on the toy’s ambient.(AU)


Assuntos
Humanos , Pré-Escolar , Desenvolvimento Infantil , Jogos e Brinquedos/psicologia , Identidade de Gênero
19.
Rev. Dep. Psicol., UFF ; 12(2/3): 69-77, maio-dez. 2000. tab
Artigo em Português | LILACS | ID: lil-501274

RESUMO

A atividade lúdica é identificada como fundamental para o desenvolvimento infantil, pois permite à criança integrar várias dimensões de sua identidade, assimilar a realidade e vivenciar papéis. Objetivou-se analisar a construção dos papéis de gênero através da situação de idade, quatro meninos e quatro meninas, e suas respectivas mães, agrupados conforme residissem em casas ou apartamentos. As entrevistas realizadas com as mães foram baseadas em roteiro especialmente elaborado, incluindo alguns itens do inventário HOME. Meninos e meninas tiveram como brinquedos/brincadeiras preferidos aqueles normalmente considerados apropriados para o seu gênero. As meninas apresentaram maior flexibilidade em relação à escolha de brinquedos/brincadeiras considerados do gênero oposto e os meninos apresentaram maior liberdade para brincar no ambiente externo. Não houve diferenciação entre estes em relação ao horário ou companhia para brincar. Comparando-se atividades lúdicas de mães e filhos, verificou-se que as primeiras brincavam mais de brincadeiras e fabricavam seus próprios brinquedos, e os últimos brincam mais com brinquedos, sendo estes industrializados. As mães das meninas estimulam mais o uso de brincadeiras e a fabricação de brinquedos do que as mães dos meninos. A qualidade do ambiente doméstico não apresentou variação. A construção dos papéis de gênero se dá simbolicamente através das atividades lúdicas e pelas contingências que envolvem a situação do brinquedo, como a estimulação por parte de suas mães em relação à forma de brincar e restrições em relação ao ambiente do brinquedo.


The act of playing has been identified as essential on child development, because it let children to integrate many different dimensions of their identity, assimilate reality, and experiment roles. This research intends to understand how do the construction of children’s roles of gender takes place through the act of playing. Eight children, four males and four females, from similar social classes, at the ages of 3 to 6 years old, and their mothers, were interviewed, stratified by living in houses or apartments. The interviews with the mothers were base on a program specially performed, including some items from HOME inventory. The favorite toys/children’s plays for boys and girls were those which are commonly considered appropriated for their gender. The girls were pliable on choosing the toys/children’s play considered appropriated for the other gender whereas the boys were more free top play outside. There were no differences on time spent or at the people the children chose to play with. It was observed that the mothers used to play with toys/children’s plays which were made and created by themselves, whereas their kids use to play with industrialized toys. The girl’s mothers stimulated more the children’s plays and the hands-made toys than boy’s mothers. The domestic environment’s quality didn’t show varieties. The construction of children’s roles of gender takes place through children’s plays and through the contingencies which involve the toy’s children situation, such as the stimulation from their mothers on how to play, and restrictions on the toy’s ambient.


Assuntos
Humanos , Pré-Escolar , Desenvolvimento Infantil , Identidade de Gênero , Jogos e Brinquedos/psicologia
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