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1.
J Intellect Disabil Res ; 68(5): 477-490, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38263598

RESUMO

BACKGROUND: Stigma towards people with intellectual disability affects various aspects of their lives, including access to employment, housing, health and social care services. Furthermore, this stigma reduces their social opportunities and is even reflected in laws that diminish their autonomy. Due to the practical significance of this issue, the aim of this research is to explore for the first time the social stigma associated with intellectual disability in a representative sample of the Spanish population. METHOD: A cross-sectional quantitative descriptive study was conducted, involving a representative sample of the population (N = 2746). The study includes descriptive analyses and hierarchical regressions to examine various dimensions of stigma, such as attitudes, attributions, and intentions of social distance. RESULTS: Medium levels of stigma are found regarding attitudes and attributions towards people with intellectual disability, while levels are medium-low concerning the intention of social distance. The most reliable indicators of stigma across its various dimensions encompass attitudes, attributions, and the intention of social distance. Factors that contribute to lower stigma include knowing someone with an intellectual disability, being willing to discuss intellectual disability with an acquaintance who has it and having a progressive political ideology. People with intellectual disability show more negative attributions towards themselves. Living with a person with an intellectual disability is another predictor of more stigmatising attitudes, but less intention of social distance. Results are mixed regarding age, gender, and educational level. CONCLUSION: Combating the stigmatisation of people with intellectual disabilities must include comprehensive actions to address attitudes, attributions and behavioural intentions. Public policies, such as national campaigns and programmes, should include contact with and open conversations about intellectual disability, and sensitivity to sociodemographic variables.


Assuntos
Deficiência Intelectual , Estigma Social , Humanos , Estudos Transversais , Espanha , Estereotipagem
2.
J Gambl Stud ; 37(3): 765-778, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33169222

RESUMO

Gambling advertising can influence attitudes and gaming behavior of adolescents and young adults (A&Y). To study the effect of advertising on the attitudes and gaming behavior of a sample of 2887 Spanish A&Y (12-22 years old), by means of a self-report assessment. On average, participants show a weak effect of advertising, however there are great variations, estimating that 11% of A&Y acknowledge being influenced by advertising and 5% recognize being severely affected. Men see themselves more impacted than women, without age differences. Those who play videogames signal a stronger effect of this kind of advertising and although these differences are not substantial in effect size, they reach statistically significance in 12 of the 13 questions assessed. A&Y who showed higher scores indicating problematic use of videogames in the IDGS9-SF, are those who indicate a greater impact of advertising on their attitudes towards gaming, as well as on the way they play or on their intention to play. These results support the idea that videogames can, albeit modestly, predispose engagement in games of chance.


Assuntos
Comportamento Aditivo , Jogo de Azar , Jogos de Vídeo , Adolescente , Publicidade , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Autorrelato , Espanha , Adulto Jovem
4.
Epidemiol Infect ; 144(9): 2011-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26758404

RESUMO

The objective of this study was to assess the effectiveness of a catheter-related bloodstream infection (CR BSI) reduction programme and healthcare workers' compliance with recommendations. A 3-year surveillance programme of CR BSIs in all hospital settings was implemented. As part of the programme, there was a direct observation of insertion and maintenance of central venous catheters (CVCs) to determine performance. A total of 38 education courses were held over the study period and feedback reports with the results of surveillance and recommendations were delivered to healthcare workers every 6 months. A total of 6722 short-term CVCs were inserted in 4982 patients for 58 763 catheter-days. Improvements of compliance with hand hygiene was verified at the insertion (87·1-100%, P < 0·001) and maintenance (51·1-72·1%, P = 0·029) of CVCs; and the use of chlorhexidine for skin disinfection was implemented at insertion (35·7-65·4%, P < 0·001) and maintenance (33·3-45·9%, P < 0·197) of CVCs. There were 266 CR BSI incidents recorded with an annual incidence density of 5·75/1000 catheter-days in the first year, 4·38 in the second year [rate ratio (RR) 0·76, 95% confidence interval (CI) 0·57-1·01] and 3·46 in the third year (RR 0·60, 95% CI 0·44-0·81). The education programme clearly improved compliance with recommendations for CVC handling, and was effective in reducing the burden of CR BSIs.


Assuntos
Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Pesquisa sobre Serviços de Saúde , Controle de Infecções/métodos , Sepse/epidemiologia , Sepse/prevenção & controle , Adulto , Idoso , Atitude do Pessoal de Saúde , Cateterismo/efeitos adversos , Cateteres Venosos Centrais/efeitos adversos , Desinfecção/métodos , Desinfecção/estatística & dados numéricos , Educação Médica , Feminino , Fidelidade a Diretrizes , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária
5.
Pharm Res ; 31(1): 182-93, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23921489

RESUMO

PURPOSE: Preparation and in vitro characterization of tamoxifen (TMX)-loaded folate-targeted nanoparticles based on disulfide bond reduced bovine serum albumin (BSA-SH) and BSA-SH/alginate-cysteine (BSA-SH/ALG-CYS) mixtures as drug delivery systems. METHODS: Folate-nanoparticles were characterized in terms of folate content, morphology, size, zeta potential, TMX load and drug release kinetics. Additionally, cell viability and cellular uptake of nanoparticles were determined using different cancer cell lines. RESULTS: Folic acid (FOL) was successfully attached to nanoparticles (ranging between 79 and170 µmol folate/g NP). Nanoparticles with 76-417 nm mean size were obtained and loaded with TMX (4.2-7.7 µg/mg NP). Zeta potential and drug extraction revealed major superficial placement of the drug, especially in the case of BSA/ALG-FOL systems. Drug release studies in the presence of surfactant showed a gradual release of the drug between 4-7 h. In general, low cytotoxicity of unloaded systems was found. Internalization of the systems was achieved and mediated by folate receptor, especially in the case of BSA NP-FOL. The administration of 10 µM TMX by TMX-FOL NP showed their efficacy as controlled TMX release systems. CONCLUSIONS: Promising anticancer action of these new TMX-loaded folate-targeted systems was demonstrated, allowing a new administration route to be studied in further in vivo studies in order to improve current TMX therapy.


Assuntos
Alginatos/química , Preparações de Ação Retardada/química , Ácido Fólico/química , Nanopartículas/química , Soroalbumina Bovina/química , Tamoxifeno/química , Alginatos/administração & dosagem , Linhagem Celular Tumoral , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/administração & dosagem , Ácido Glucurônico/administração & dosagem , Ácido Glucurônico/química , Células HeLa , Ácidos Hexurônicos/administração & dosagem , Ácidos Hexurônicos/química , Humanos , Células MCF-7 , Nanopartículas/administração & dosagem , Tamanho da Partícula , Soroalbumina Bovina/administração & dosagem , Tamoxifeno/administração & dosagem
6.
Pharm Res ; 31(5): 1264-74, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24218224

RESUMO

PURPOSE: In vivo evaluation of tamoxifen (TMX)-loaded folate-targeted nanoparticles prepared from a mixture of disulphide bond reduced bovine serum albumin (BSA-SH) and alginate-cysteine (ALG-CYS) as targeted delivery systems of TMX to tumour tissues. METHODS: TMX in solution, TMX included into folate-nanoparticles and their non-targeted analogues were intravenously administered to nude mice carrying xenograft MCF-7 tumours. The antitumor activity of these systems was characterized in terms of tumour growth rate, histological and immunohistochemical analysis of tumour tissues and TMX biodistribution. RESULTS: TMX-folate-attached nanoparticles caused tumour remission whereas free TMX or TMX-non-targeted nanoparticles could only stop the tumour development. The histological evaluation of tumour tissues showed that those treated with folate-conjugated systems presented the most quiescent and disorganized structures. Additionally, the lowest concentrations of TMX accumulated in non-targeted organs were also found after administration of the drug using this formulation. CONCLUSIONS: This study demonstrated that TMX-loaded folate-targeted systems were capable of reaching tumour sites, so enhancing the in vivo anticancer action of TMX, and allowing a new administration route to be applied and some of the current TMX therapy problems to be overcome.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ácido Fólico/química , Nanopartículas , Tamoxifeno/uso terapêutico , Albuminas/química , Alginatos/química , Animais , Neoplasias da Mama/patologia , Cisteína/química , Dissulfetos/química , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Células MCF-7 , Camundongos , Camundongos Nus , Tamoxifeno/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Avian Pathol ; 43(2): 172-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24689431

RESUMO

The aim of this study was to determine the presence of virulence genes and antibiotic resistance profiles in 164 Escherichia coli strains isolated from birds (feral pigeons, hybrid ducks, house sparrows and spotless starlings) inhabiting urban and rural environments. A total of eight atypical enteropathogenic E. coli strains were identified: one in a house sparrow, four in feral pigeons and three in spotless starlings. Antibiotic resistance was present in 32.9% (54) of E. coli strains. The dominant type of resistance was to tetracycline (21.3%), ampicillin (19.5%) and sulfamethoxazole (18.9%). Five isolates had class 1 integrons containing gene cassettes encoding for dihydrofolate reductase A (dfrA) and aminoglycoside adenyltransferase A (aadA), one in a feral pigeon and four in spotless starlings. To our knowledge, the present study constitutes the first detection of virulence genes from E. coli in spotless starlings and house sparrows, and is also the first identification worldwide of integrons containing antibiotic resistance gene cassettes in E. coli strains from spotless starlings and pigeons.


Assuntos
Doenças das Aves/epidemiologia , Columbidae/microbiologia , Patos/microbiologia , Escherichia coli Enteropatogênica/genética , Pardais/microbiologia , Estorninhos/microbiologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Doenças das Aves/microbiologia , Reservatórios de Doenças , Farmacorresistência Bacteriana/genética , Escherichia coli Enteropatogênica/efeitos dos fármacos , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enteropatogênica/patogenicidade , Integrons/genética , Testes de Sensibilidade Microbiana/veterinária , Espanha/epidemiologia , Fatores de Virulência/genética
8.
Heliyon ; 10(14): e34174, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39108863

RESUMO

In the last few years, the exploitation of deep-sea regions for minerals extraction raised international attention as an economically viable source for the mining industry. However, most of these minerals are found close to sensitive ecosystems that can be harmed by mining activities. Given the potential impact, there is a need for the establishment of best practices towards the adoption of preventive strategies for the sustainable management and exploitation of deep-sea environments. To accomplish this objective, numerical models have proven to be reliable tools to support decision-making. In the present study, a high-resolution eddy-resolving ocean numerical model was configured and integrated with a semi-Lagrangian model aiming to map the transport of rock-fragments associated with mining activities. The model was applied to an area rich in polymetallic sulphides at the Northern Mid-Atlantic Ridge (NMAR). Model results showed that local topography and circulation dynamics played an important role for the dispersion and settling of the rock-fragments. In the presence of local submesoscale processes, the residence time do not follow the neutral relation H/vs. It was demonstrated that, depending on the local hydrodynamics, rock-fragments released at sub-surface depth can impact wider areas, with a predicted impact on pelagic and benthic organisms.

9.
Eur J Cancer Care (Engl) ; 22(3): 314-25, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23279127

RESUMO

Childhood cancer is a life-threatening disease and the cause of great stress for children who suffer from its diagnosis and treatment. The aim of this study was to verify, through meta-analytical tools, whether children in active treatment for cancer differ in their psychological adjustment from healthy children. Ten studies fulfilled the inclusion criteria for the meta-analytic approach. A fixed effects model did not yield significant results, suggesting that there is no evidence for a difference in psychological adjustment between ill and healthy children, inasmuch as the former seem to adjust as well as the latter. Some methodological aspects are also considered, including issues related to the definition of psychological adjustment and its operationalisation and to the relative scarcity of published articles in this particular realm. Moreover, suggestions for future studies are discussed.


Assuntos
Adaptação Psicológica , Neoplasias/psicologia , Adolescente , Criança , Nível de Saúde , Humanos , Ajustamento Social
10.
Mar Pollut Bull ; 193: 115168, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37329738

RESUMO

Marine litter is a growing global problem with serious environmental, economic, social, and health threats. Understanding the socio-economic factors that influence the types and amounts of litter is of utmost importance. In this study, an integrative analysis of the socio-economic factors that characterize the beach litter distribution in continental Portugal and the Azores archipelago was conducted via a cluster analysis, implementing a novel technique to support the difficult task of marine litter characterization. The results highlighted that the most abundant beach litter material is plastic (92.9 %), followed by paper (2.2 %), wood (1.5 %), and metal (1.3 %). The majority of the items could not be attributed to a specific source (46.5 %). The remaining were attributed to public litter (34.5 % of total aggregated items), fishing (9.8 %), sewage-related debris (6.4 %) and shipping (2.2 %). The top-three beach litter categories were small plastic pieces (0-2.5 cm, 43.5 %), cigarette butts (30.1 %), and medium plastic pieces (2.5-50 cm, 26.4 %). A positive relation between both municipality environment expenditures and population density and the quantity and typology of litter was found. Beach litter quantity and categories were also associated with specific economic sectors, as well as with geographical/hydrodynamic conditions, demonstrating the utility of the technique and its applicability to other regions.


Assuntos
Monitoramento Ambiental , Resíduos , Portugal , Resíduos/análise , Monitoramento Ambiental/métodos , Praias , Plásticos
11.
J Healthc Qual Res ; 38(1): 20-25, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35835633

RESUMO

BACKGROUND: The impact of COVID-19 in families and patients with congenital diaphragmatic hernia (CDH) is unknown, this situation has generated uncertainty not only in family members but also in the optimal outpatient follow-up. Telehealth has become a fundamental tool for the follow-up during the pandemic. The objective of this survey is to evaluated the impact of SARS-CoV-2 in families and patients with CDH and the satisfaction with telematic follow-up. METHODS: Telephone survey of patient's caregivers with CHD, aged 1-16 years, followed in neonatal surgery outpatients, from January 31, 2020 to November 15, 2020. The ethical clearance for this study was taken from the Clinical Research Ethics Committee of our Research Institute vide letter number VHIR/239283/01.01.2021. RESULTS: 81 surveys of 100 patients with active follow-up were carried out. There were no refusals in any contacted parents. There were 30 contacts (37%), 44.8% at school and 27.6% from cohabiting family members. Four infections (4.9%) were diagnosed, half symptomatic. In 40 patients (49.4%) the follow-up was telematic, with a mean score of 3.1±1.3 out of 5. For future controls, 65% prefer presential follow-up, 25% alternate and 10% telematics. 50.6% reported greater anxiety and 34.6% (28/81) extreme measures of isolation, being more accentuated in the group of 3-6 years (p<0.05). CONCLUSION: The impact of COVID19 in patients with CHD is not greater than in the general pediatric population. Although the incorporation of the telehealth was well valued, most of the caregivers prefer the face-to-face outpatient follow-up.


Assuntos
COVID-19 , Hérnias Diafragmáticas Congênitas , Recém-Nascido , Humanos , Criança , SARS-CoV-2 , Hérnias Diafragmáticas Congênitas/diagnóstico , Hérnias Diafragmáticas Congênitas/cirurgia , COVID-19/epidemiologia , Seguimentos , Pandemias , Satisfação do Paciente , Satisfação Pessoal
12.
Epidemiol Infect ; 139(1): 91-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20525413

RESUMO

Early detection of highly pathogenic avian influenza (HPAI) in its natural reservoirs is a prerequisite for preventing disease spread to humans. The risk of introduction of H5N1 HPAI was assessed in order to design a risk-based surveillance system in Spain. Areas at highest risk for H5N1 HPAI followed a northeast-southwest direction, with two significant clusters located in the north and the southwest of the country. Most (83%) of the veterinary units (VUs) obtained fewer samples than would have been expected if samples had been collected using a risk-based design. In October 2009, a HPAI outbreak was reported for the first time in a Spanish layer farm located in a VU at high risk for HPAI, but no samples were collected. This risk-based surveillance approach will increase the cost-effectiveness of HPAI surveillance in Spain and can be easily extended to and adopted by other countries and regions throughout the world.


Assuntos
Anseriformes , Reservatórios de Doenças/veterinária , Virus da Influenza A Subtipo H5N1 , Influenza Aviária/epidemiologia , Migração Animal , Animais , Animais Selvagens , Aves , Surtos de Doenças/prevenção & controle , Surtos de Doenças/veterinária , Influenza Aviária/virologia , Medição de Risco , Espanha/epidemiologia
13.
Epidemiol Infect ; 139(1): 99-104, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20546634

RESUMO

Highly pathogenic avian influenza (HPAI) has devastating consequences for the poultry industry of affected countries. Control of HPAI has been impaired by the role of wildlife species that act as disease reservoirs and as a potential source of infection for domestic populations. The reproductive ratio (R0) of HPAI was quantified in nine clusters of outbreaks detected in wild birds in Europe (2005-2008) for which population data were not available. The median value of R0 was similar (1·1-3·4) for the nine clusters and it was about tenfold smaller than the value estimated for poultry in The Netherlands in 2003. Results presented here will be useful to parameterize models for spread of HPAI in wild birds and to design effective prevention programmes for the European poultry sector. The method is suitable to estimate R0 in the absence of population data, which is a condition typically observed for many wildlife and certain domestic species and systems.


Assuntos
Animais Selvagens , Virus da Influenza A Subtipo H5N1 , Influenza Aviária/epidemiologia , Animais , Aves , Análise por Conglomerados , Reservatórios de Doenças , Europa (Continente)/epidemiologia , Influenza Aviária/transmissão , Influenza Aviária/virologia , Modelos Biológicos
14.
J Microencapsul ; 28(5): 417-29, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21736526

RESUMO

Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL) polymers using the spray-drying technique. Morphology, size distribution, drug encapsulation efficiency, thermal degradation and drug release were characterized. MCF7 cells were employed to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The particle size was in the range 0.8-1 µm. The incorporation efficiency of PTX was more than 80% in all NPs obtained. In vitro drug release took place during 35 days, and drug release rates were in the order PCL > PLGA 50:50 > PLGA 75:25. Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs demonstrated the release of the drug block cells in the G2/M phase. All PTX-loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX-loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower than 20%.


Assuntos
Nanopartículas/química , Paclitaxel/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fase G2 , Humanos , Nanopartículas/uso terapêutico , Paclitaxel/farmacocinética , Poliésteres
16.
Appetite ; 55(3): 478-83, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20801177

RESUMO

The aim of this study was to gain information concerning apple and peach consumption frequency within different European countries in relation to age and gender. The survey was a part of a complex experiment with the aim of evaluating consumers' preferences towards new varieties, and the data is based on the self-reported declarations of respondents, male and female, between 15 and 70 years old. 4271 consumers from 7 European countries were invited to supply information about their apple consumption habits, whereas 499 respondents from 5 countries answered questions relating to frequency of peach and nectarine consumption. In both, the apple and the peach surveys, data analysis of declared intake showed significant differences between nationalities. The highest apple consumption was in Poland, where over 55% declared a consumption of more than 5 apples per week. In comparison, Italian consumers most often indicated eating 3-5 apples per week (39.3%). The lowest apple consumption was in the Netherlands and Spain. In the case of peaches, the highest consumption was indicated in France where 48% of respondents declared a peach consumption of 3-5 per week with 40% eating more than 5 fruits per week. The lowest peach intake was declared in Germany. Irrespective of country women were shown to eat more apples that men. Furthermore, the group of older people (61-70 years) consume apples more often than the adult group (36-60), while within the youngest group of consumers (16-35) eating apples was not at all popular. As with apples females declared a higher peach consumption, and again significantly lower fruit consumption by the youngest group (16-35) was indicated. Although the availability of fruit at the market remains a prime factor in determining apple and peach consumption, our survey confirmed the trends of declining this popular fruit intake by the younger generation, as well as the persistent tendency of lower frequency of fruit consumption among men than women.


Assuntos
Comportamento Alimentar , Frutas , Malus , Prunus , Adolescente , Adulto , Fatores Etários , Idoso , Inquéritos sobre Dietas , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Fatores Sexuais , Adulto Jovem
17.
Sci Total Environ ; 707: 135792, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31865079

RESUMO

An increase in anthropogenic activities in coastal regions can put at risk their flora and fauna and their ecosystem services. Therefore, it is important to evaluate possible impacts. In particular, we need to understand the links between contaminants concentrations and the hydrodynamic patterns of these highly productive regions to anticipate the effects of contaminants in the environment. Towards that aim there is the need to carry out regular campaigns to monitor the evolution of the coastal systems. In this work we analyse in-situ measurements of physico-chemical parameters, and look for possible relations between observed contaminants patterns and estuarine hydrodynamics. Data collected in the Douro estuary, one of the main estuarine regions of the Iberian western coast, revealed the presence of 5 hazardous and noxious substances (HNS), 14 polycyclic aromatic hydrocarbons (PAHs) and 6 trace metals in water and sediment samples. Water temperature and salinity analysis revealed a strong variability, which can affect the water solubility properties and the organisms' tolerance to certain toxins. A relationship between the salinity and the HNS and PAHs concentrations was found, caused by the existence of a salt-wedge that triggers the salting-out effect. Sinker contaminants (PAHs and trace metals) can be re-suspended both during low and high flow conditions associated with the salt-wedge and with strong river flows. Floater contaminants (HNS) are completely depended on the tide, which has the capacity to distribute them through the entire estuary, during low river flow regimes. However, strong river flows, with associated river plumes, can distribute both sinker and floater contaminants to the coastal region trapping them over the inner-shelf. The results clearly show that hydrodynamic patterns are a major driver for contaminants dispersion and pathways in coastal areas, inducing harmful effects to the flora and fauna and, consequently, to the ecosystem services of these regions.

18.
Oncogene ; 39(13): 2756-2771, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015486

RESUMO

Aldehyde dehydrogenases (ALDHs) are multifunctional enzymes that oxidize diverse endogenous and exogenous aldehydes. We conducted a meta-analysis based on The Cancer Genome Atlas and Gene Expression Omnibus data and detected genetic alterations in ALDH1A1, ALDH1A3, or ALDH3A1, 86% of which were gene amplification or mRNA upregulation, in 31% of nonsmall cell lung cancers (NSCLCs). The expression of these isoenzymes impacted chemoresistance and shortened survival times in patients. We hypothesized that these enzymes provide an oxidative advantage for the persistence of NSCLC. To test this hypothesis, we used genetic and pharmacological approaches with DIMATE, an irreversible inhibitor of ALDH1/3. DIMATE showed cytotoxicity in 73% of NSCLC cell lines tested and demonstrated antitumor activity in orthotopic xenografts via hydroxynonenal-protein adduct accumulation, GSTO1-mediated depletion of glutathione and increased H2O2. Consistent with this result, ALDH1/3 disruption synergized with ROS-inducing agents or glutathione synthesis inhibitors to trigger cell death. In lung cancer xenografts with high to moderate cisplatin resistance, combination treatment with DIMATE promoted strong synergistic responses with tumor regression. These results indicate that NSCLCs with increased expression of ALDH1A1, ALDH1A3, or ALDH3A1 may be targeted by strategies involving inhibitors of these isoenzymes as monotherapy or in combination with chemotherapy to overcome patient-specific drug resistance.


Assuntos
Família Aldeído Desidrogenase 1/antagonistas & inibidores , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído Oxirredutases/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Retinal Desidrogenase/antagonistas & inibidores , Idoso , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Família Aldeído Desidrogenase 1/genética , Família Aldeído Desidrogenase 1/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Alcinos/farmacologia , Alcinos/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Glutationa/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Retinal Desidrogenase/genética , Retinal Desidrogenase/metabolismo , Compostos de Sulfidrila/farmacologia , Compostos de Sulfidrila/uso terapêutico , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
19.
An Pediatr (Barc) ; 71(4): 284-90, 2009 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-19713162

RESUMO

UNLABELLED: The etiology of preterm birth is difficult to classify. It is usually divided into three clinical types according to its clinical presentation: medically indicated; caused by ruptured membranes; and spontaneous or idiopathic. However, this classification is controversial, imprecise and can result in multiple interpretations when applied. OBJECTIVE: To design an etiologically based classification of preterm birth, and to design a system to easily assign each case during the perinatal period. METHODS: Review of literature, qualitative analysis using consensus methods through nominal group technique, and quantitative analysis of a pilot study using a first version of the algorithm. RESULTS: A classification is made to establish a general division between the "primary cause" and "associated causes" of preterm birth, that allows remote causes or risk factors to be included. The primary cause includes seven categories: inflammatory (ruptured membranes and related); vascular (intrauterine growth restriction and related); maternal-local; maternal-systemic; fetal pathology; fetal distress; idiopathic. The medically indicated preterm birth is defined as a previous or independent category and so is compatible with the other, previously mentioned causes . An algorithm was designed to make it easier to classify the primary cause of preterm birth using a flowchart. CONCLUSIONS: A pragmatic classification of preterm birth is proposed that may help to achieve better precision and agreement between clinicians.


Assuntos
Algoritmos , Nascimento Prematuro/classificação , Nascimento Prematuro/etiologia , Humanos , Recém-Nascido
20.
Transplant Proc ; 40(2): 351-4, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18374064

RESUMO

Assessing islet cellular composition and beta cell viability using Flow Cytometry (FC) and Laser Scanning Cytometry (LSC) may aid in determining the transplant quality of islets. Human islets (2500 IEQ, n = 44, purity >or=80%) dissociated into a single cell suspension were stained with ductal marker CA19, with Newport Green (NG) and FluoZin3 (FL3) for beta-cell identification, with TMRE to assess mitochondrial membrane potential, with DAPI to identify live vs. dead cells, and with Annexin-V/DAPI to differentiate apoptotic and necrotic cells. For LSC, cell preparations (n = 9) were stained for insulin (beta-cells), glucagon (alpha-cells), somatostatin (delta cells), and pancreatic polypeptide (ppp cells). Fluorescence microscopy (EtBr/FDA) and insulin response were also measured. DAPI- staining was 73.78% +/- 1.37, while EtBr/FDA was 96% +/- 0.48. 52.5% +/- 3.73 of all cells were NG+, of which 58.08% +/- 2.61 were NG+/TMRE+. Annexin-V/DAPI staining (n = 26) showed 13.8% +/- 0.89 apoptotic, 27.2% +/- 2.0 necrotic, and 51.9% +/- 2.22 live cells. 26.0% +/- 5.19 of cells were CA19 positive (n = 17), of which 45.5% +/- 4.37 were also TMRE+, and 5.2% +/- 1.2 of the TMRE+ were also NG+/CA19+. NG and FL3 showed similar staining (n = 8). Comparison of short-term (or=3 days) culture showed similar TMRE+/NG+ averages, albeit lower percentages of live (36.4% vs 51.9%), and higher percentages of apoptotic (19.2% vs 13.8%) and necrotic cells (37.4% vs 27.2%) for long-term, as determined by Annexin-V staining. LSC resulted in 54.17% +/- 4.62 beta-cells, 33.33% +/- 4.16 alpha-cells, 8.75% +/- 2.5 delta-cells, and 3.75% +/- 0.79 ppp cells. There is no significant difference between insulin positive cells and NG positive cells (P

Assuntos
Citometria de Fluxo/métodos , Ilhotas Pancreáticas/citologia , Citometria de Varredura a Laser/métodos , Técnicas de Cultura de Células , Separação Celular/métodos , Sobrevivência Celular , Corantes , Humanos , Células Secretoras de Insulina/citologia
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