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1.
J Toxicol Environ Health A ; 87(4): 133-149, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-37997947

ABSTRACT

Environmental management relies on many types of information before making decisions regarding remediation, restoration, or other land use decisions, including ecological data, such as risks to species, populations, communities, and ecosystems. The aim of this investigation was to describe the ecological information required within the context of making environmental decisions and providing visual communication tools for regulators, conservationists, and the public to understand the risk to ecological resources on- and off-site. It is suggested that ecological information used in environmental decisions is required to be transparent throughout the planning and execution of a project, which needs to include: 1) ecological information and evaluations within development areas or units (in this case, watersheds), and 2) resources in adjacent areas (Buffer Zones) that might be affected. The Melton Valley administrative watershed (Oak Ridge Reservation, TN) is used as a case study because this site still has active facility development and environmental remediation, and there are important ecological resources on and off-site. Data indicate that although there are important resources on Melton Valley administrative watershed, there are also significant resources in the Buffer Zone around the watershed. Compared to the Melton Valley administrative watershed, the Buffer Zone contains more Interior (and Buffer) Forest and greater value resources. The point is made that when remediation, restoration, or development occurs, it is equally important to consider resources that are adjacent to the site in a Buffer Zone, particularly when remediation and development might continue for many years or decades.


Subject(s)
Ecosystem , Environmental Restoration and Remediation , Conservation of Natural Resources
2.
Article in English | LILACS-Express | LILACS | ID: biblio-1535276

ABSTRACT

Objective: To analyze the behavior of pesticide poisoning associated with lethality in rural and urban populations in Colombia from 2007 to 2017. Methodology: Retrospective observational study that included a descriptive cross-sectional study and an ecological design that analyzed aggregate measures of morbidity, mortality, and risk attributable to the population in rural and urban areas. In the cross-sectional study, the relative risk was estimated to measure the factors associated with lethality among intoxications using Poisson regression with logarithmic function. For the time series, the trends were established with simple linear regression, and the seasonal decomposition was performed using the multiplicative model. Autocorrelations were tested using the Box-Ljung statistic. Results: Between 2007-2017; 89 490 cases were reported. The Morbidity due to poisoning showed a higher proportion in the rural population 36.03 cases per 100 000; this indicator was three times higher than in urban areas (12.33 cases per 100 000). The mortality rates in rural and urban areas were 1.00 and 0.13 cases per 100 000, respectively. The relative risk of fatality in case of intoxication was associated with the intention of suicide in the rural population Relative Risk (RR): 5.9 (95% CI: 5.0-6.9). Conclusion: A higher proportion of lethality associated with these events occurred in populations living in rural areas and reporting cases of suicidal intent. In addition, morbidity and mortality due to pesticide poisoning had the highest proportion in rural areas and a growing trend over time.


Objetivo: Analizar el comportamiento de las intoxicaciones por plaguicidas en poblaciones rurales y urbanas asociadas a la letalidad en Colombia durante 2007-2017. Metodología: Estudio observacional retrospectivo que incluyó: un estudio descriptivo transversal y un diseño ecológico que analizó medidas agregadas de morbilidad, mortalidad y riesgo atribuibles a la población en áreas rurales y urbanas. En el estudio transversal se estimó el riesgo relativo para medir los factores asociados a la letalidad entre las intoxicaciones mediante regresión de Poisson con función logarítmica. Para la serie de tiempo, las tendencias se establecieron con regresión lineal simple y la descomposición estacional se realizó mediante el modelo multiplicativo. Las autocorrelaciones se probaron mediante el estadístico Box-Ljung. Resultados: Entre 2007-2017; Se notificaron 89 490 casos. La Morbilidad por intoxicación presentó mayor proporción en la población rural 36,03 casos por 100 000; este indicador fue tres veces mayor que en las áreas urbanas (12,33 casos por 100 000). Las tasas de mortalidad en el área rural y urbana fueron de 1,00 y 0,13 casos por 100 000, respectivamente. El riesgo relativo de fatalidad en caso de intoxicación se asoció con la intención de suicidio en la población rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusión: Una mayor proporción de letalidad asociada a estos eventos ocurrió en poblaciones que viven en áreas rurales y reportan casos de intención suicida. Además, la morbilidad y mortalidad por intoxicación por plaguicidas tuvo la mayor proporción en las zonas rurales y una tendencia creciente en el tiempo.


Objetivo: Analisar o comportamento das intoxicações por agrotóxicos em populações rurais e urbanas associadas à letalidade na Colômbia durante 2007-2017. Metodologia: Estudo observacional retrospectivo que incluiu: estudo transversal descritivo e delineamento ecológico que analisou medidas agregadas de morbidade, mortalidade e risco atribuíveis à população em áreas rurais e urbanas. No estudo transversal, o risco relativo foi estimado para medir os fatores associados à letalidade entre as intoxicações por meio da regressão de Poisson com função logarítmica. Para as séries temporais, as tendências foram estabelecidas com regressão linear simples e a decomposição sazonal foi realizada usando o modelo multiplicativo. As autocorrelações foram testadas usando a estatística Box-Ljung. Resultados: Entre 2007-2017; 89.490 casos foram notificados. A Morbidade por intoxicação apresentou maior proporção na população rural 36,03 casos por 100.000; este indicador foi três vezes superior ao das zonas urbanas (12,33 casos por 100 000). As taxas de mortalidade nas áreas rural e urbana foram de 1,00 e 0,13 casos por 100.000 habitantes, respectivamente. O risco relativo de fatalidade em caso de intoxicação associou-se à intenção de suicídio na população rural RR: 5,9 (IC 95%: 5,0-6,9). Conclusão: Maior proporção de letalidade associada a esses eventos ocorreu em populações residentes em áreas rurais e com relato de casos de intenção suicida. Além disso, a morbimortalidade por intoxicação por agrotóxicos teve maior proporção na zona rural e tendência crescente ao longo do tempo.

3.
J Toxicol Environ Health A ; 86(15): 501-517, 2023 08 03.
Article in English | MEDLINE | ID: mdl-37335075

ABSTRACT

Pressure from expanding populations has resulted in a need for protection, reclamation, and restoration of damaged land to productive, beneficial health uses. The objective of this investigation was to 1) compare land cover on the Department of Energy (DOE) Oak Ridge Reservation (ORR) with the surrounding region, 2) select an indicator to evaluate ORR's protection of ecological resources, and 3) develop and implement a method to compare the amount of the indicator on ORR with the regions using National Land Cover Database (NLCD). Data demonstrated that ORR has a higher % of forests (deciduous, coniferous, mixed) than the 10 km and 30 km areas surrounding ORR, suggesting that obligations are being met to protect the ecology and environment. The findings also indicate that the interior forest at ORR is fragmented more than is the interior forest in the 30 km buffer zone, suggesting a need for DOE and managers of other lands to take into consideration the importance of intact interior forest when developing land or planning roads. The study describes the basis for specific ecological parameters such as interior forest that are important to consider when planning and executing remediation, restoration, and other management actions.


Subject(s)
Conservation of Natural Resources , Forests , Conservation of Natural Resources/methods , Databases, Factual , Ecosystem
4.
Cell Death Dis ; 14(2): 135, 2023 02 17.
Article in English | MEDLINE | ID: mdl-36797281

ABSTRACT

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.


Subject(s)
Endothelial Cells , Melanoma , Uveal Neoplasms , beta Catenin , beta Catenin/genetics , beta Catenin/metabolism , Cadherins/genetics , Cadherins/metabolism , Endothelial Cells/metabolism , Melanoma/pathology , Proteomics , Uveal Neoplasms/pathology , Transcription Factor 4/metabolism
5.
J Pathol ; 259(3): 318-330, 2023 03.
Article in English | MEDLINE | ID: mdl-36484652

ABSTRACT

Vasculogenic mimicry (VM) describes the ability of highly aggressive tumor cells to develop pseudovascular structures without the participation of endothelial cells. PARP1 is implicated in the activation of hypoxia-inducible factors, which are crucial in tumor neovascularization. We have explored the role of hypoxia and PARP inhibition in VM. In uveal melanoma xenografts, the PARP inhibitor olaparib improved in vivo pericyte coverage specifically of VM channels. This was concomitant with reduced metastasis in olaparib-treated VM+ tumors. PARP inhibition and hypoxia modulated melanoma tube formation in vitro, inducing a more sparse and regular tubular architecture. Whole-transcriptome profiling revealed that olaparib treatment under hypoxic conditions modulated the expression of genes implicated in vasculogenesis during tube formation, enhancing the endothelial-like phenotype of VM+ uveal melanoma cells. PARP inhibition, especially during hypoxia, upregulated PDGFß, which is essential for pericyte recruitment. Our study indicates that PARP inhibitors may enhance the endothelial characteristics of VM+ cells, modulate pericyte coverage, and reduce metastatic spread in VM+ melanoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Subject(s)
Melanoma , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Endothelial Cells/metabolism , Pericytes/metabolism , Melanoma/drug therapy , Melanoma/metabolism , Neovascularization, Pathologic/pathology , Phenotype , Cell Line, Tumor
6.
Medicina (Kaunas) ; 58(8)2022 Aug 19.
Article in English | MEDLINE | ID: mdl-36013592

ABSTRACT

Background and Objectives: Particulate Matter (PM), particles of variable but small diameter can penetrate the respiratory system via inhalation, causing respiratory and/or cardiovascular diseases. This study aims to evaluate the association of environmental particulate matter (PM2.5) and black carbon (BC) with respiratory health in users of different transport modes in four roads in Bogotá. Materials and Methods: this was a mixed-method study (including a cross sectional study and a qualitative description of the air quality perception), in 300 healthy participants, based on an exploratory sequential design. The respiratory effect was measured comparing the changes between pre- and post-spirometry. The PM2.5 and black carbon (BC) concentrations were measured using portable devices. Inhaled doses were also calculated for each participant according to the mode and route. Perception was approached through semi-structured interviews. The analysis included multivariate models and concurrent triangulation. Results: The concentration of matter and black carbon were greater in bus users (median 50.67 µg m-3; interquartile range (-IR): 306.7). We found greater inhaled dosages of air pollutants among bike users (16.41 µg m-3). We did not find changes in the spirometry parameter associated with air pollutants or transport modes. The participants reported a major sensory influence at the visual and olfactory level as perception of bad air quality. Conclusions: We observed greater inhaled doses among active transport users. Nevertheless, no pathological changes were identified in the spirometry parameters. People's perceptions are a preponderant element in the assessment of air quality.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/adverse effects , Carbon , Colombia , Cross-Sectional Studies , Environmental Exposure/adverse effects , Humans , Particulate Matter/adverse effects
7.
Ciênc. Saúde Colet. (Impr.) ; 27(8): 3053-3061, ago. 2022.
Article in English | LILACS-Express | LILACS | ID: biblio-1384466

ABSTRACT

Abstract COVID-19 has challenged health professionals in widely divergent areas, including innovation of practice, communication, multidisciplinary activities, broader use of technology, and adaptability. The role of the dietitian and other health professionals in dealing with the evolving crisis might be considered essential in treating patients. Given the limited access to various food options, nutrition screening and assessment deserves a high priority to complete a comprehensive nutrition evaluation, identify nutrition risks, prioritize care, and provide early nutrition intervention and support to all patients with or who have had, COVID-19 and are experiencing ongoing symptoms. Such an intervention would benefit the patients and the health system by reducing the length of hospital stay, ameliorating further complications, limiting hospital readmission, enhancing recovery, and assisting in the management of comorbidities and their metabolic alterations. This brief overview outlines the essential role of nutrition intervention and support as part of an integrated, multidisciplinary treatment program for the care of COVID-19 patients during the pandemic. Restrictive movements have changed consultative approaches, and the importance of Telenutrition for the effective communication of health status and recommendations.


Resumo A COVID-19 desafiou profissionais de saúde em diversas áreas, incluindo inovação da prática, comunicação, atividades multidisciplinares, uso amplo de tecnologia e adaptabilidade. O papel do nutricionista e de outros profissionais de saúde para lidar com a crise em expansão pode ser considerado essencial no tratamento de pacientes. Devido ao acesso limitado a várias opções de alimentos, a triagem e a avaliação nutricional devem ser priorizadas para a obtenção de uma avaliação nutricional abrangente, a fim de identificar riscos nutricionais, priorizar atendimento e possibilitar a intervenção nutricional precoce e o apoio a todos os pacientes com, ou que tiveram, COVID-19 e apresentem sintomas contínuos. Tal intervenção traria grande benefício aos pacientes e ao sistema de saúde, ao reduzir o tempo de internação, amenizar complicações posteriores, limitar a readmissão hospitalar, potencializar a recuperação e auxiliar no manejo das comorbidades e suas alterações metabólicas. Esta breve descrição elucida o papel essencial da intervenção nutricional e do apoio como parte de um programa de tratamento multidisciplinar para o cuidado de pacientes com COVID-19 durante a pandemia. Movimentos restritivos mudaram as abordagens consultivas e a importância da telenutrição para a comunicação eficaz do estado de saúde e das recomendações.

8.
Cien Saude Colet ; 27(8): 3053-3061, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35894318

ABSTRACT

COVID-19 has challenged health professionals in widely divergent areas, including innovation of practice, communication, multidisciplinary activities, broader use of technology, and adaptability. The role of the dietitian and other health professionals in dealing with the evolving crisis might be considered essential in treating patients. Given the limited access to various food options, nutrition screening and assessment deserves a high priority to complete a comprehensive nutrition evaluation, identify nutrition risks, prioritize care, and provide early nutrition intervention and support to all patients with or who have had, COVID-19 and are experiencing ongoing symptoms. Such an intervention would benefit the patients and the health system by reducing the length of hospital stay, ameliorating further complications, limiting hospital readmission, enhancing recovery, and assisting in the management of comorbidities and their metabolic alterations. This brief overview outlines the essential role of nutrition intervention and support as part of an integrated, multidisciplinary treatment program for the care of COVID-19 patients during the pandemic. Restrictive movements have changed consultative approaches, and the importance of Telenutrition for the effective communication of health status and recommendations.


Subject(s)
COVID-19 , Nutritionists , Health Personnel , Humans , Nutrition Assessment , Pandemics/prevention & control
9.
Cancers (Basel) ; 14(11)2022 May 31.
Article in English | MEDLINE | ID: mdl-35681719

ABSTRACT

Hyperoxia is used in order to counteract hypoxia effects in the TME (tumor microenvironment), which are described to boost the malignant tumor phenotype and poor prognosis. The reduction of tumor hypoxic state through the formation of a non-aberrant vasculature or an increase in the toxicity of the therapeutic agent improves the efficacy of therapies such as chemotherapy. Radiotherapy efficacy has also improved, where apoptotic mechanisms seem to be implicated. Moreover, hyperoxia increases the antitumor immunity through diverse pathways, leading to an immunopermissive TME. Although hyperoxia is an approved treatment for preventing and treating hypoxemia, it has harmful side-effects. Prolonged exposure to high oxygen levels may cause acute lung injury, characterized by an exacerbated immune response, and the destruction of the alveolar-capillary barrier. Furthermore, under this situation, the high concentration of ROS may cause toxicity that will lead not only to cell death but also to an increase in chemoattractant and proinflammatory cytokine secretion. This would end in a lung leukocyte recruitment and, therefore, lung damage. Moreover, unregulated inflammation causes different consequences promoting tumor development and metastasis. This process is known as protumor inflammation, where different cell types and molecules are implicated; for instance, IL-1ß has been described as a key cytokine. Although current results show benefits over cancer therapies using hyperoxia, further studies need to be conducted, not only to improve tumor regression, but also to prevent its collateral damage.

10.
Neurotoxicology ; 90: 112-120, 2022 05.
Article in English | MEDLINE | ID: mdl-35306101

ABSTRACT

Colombia is one of the largest pesticide consumers in South America. These products have a variety of negative consequences on the health of rural populations, especially neurocognitive disorders in children. In this work, the prenatal and postnatal exposure to pesticides was evaluated and the association between the cognitive capacity of school-age children in rural areas of the city of Bogotá, Colombia, investigated. Separate multiple linear regression models were used to evaluate associations of pesticide exposure measures and WISC-IV scales, adjusted for child sex, maternal educational attainment, growth retardation, and effect modification explored by sex, using a cross products term of 232 children between the ages of 7 and 10. It was found that among all children, pesticide exposure at school was associated with a worse working memory index (ß = -3.40; 95%CI; -6.6; -0.2) and a worst verbal comprehension index (ß = -3.2; 95%CI; -6.5; -0.2). Among girls, pesticide use at home was associated with a worse processing speed index (ß = -5.1; 95% CI; -10.1; -0.20) but not among boys (ß = 1.73; 95% CI; -2.6; 6.9). This revealed an association between the prenatal and postnatal exposure reported and some IQ sub-indices of children aged between 7 and 10 years residing in the rural areas of Usme and Sumapaz in the city of Bogotá, Colombia.


Subject(s)
Pesticides , Prenatal Exposure Delayed Effects , Child , Cognition , Colombia/epidemiology , Female , Humans , Male , Pesticides/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/epidemiology , Rural Population , Wechsler Scales
11.
Environ Sci Pollut Res Int ; 28(40): 57275-57287, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34086176

ABSTRACT

The aim of this study was to determine the association between the concentrations of intradomiciliary PM2.5, CO, and BC and alterations in respiratory function parameters in a population living in rural dwellings in Bogotá, Colombia. For this cross-sectional study, people were recruited from the rural areas of the localities of Usme and Sumapaz in Bogotá. In total, 68 participants were recruited by means of nonrandom sampling. Indoor air monitoring of PM2.5, BC, and CO was carried out. Additionally, evaluations of pulmonary function were performed using spirometry. The variables of pulmonary function were included in a multiple linear regression by successive steps and adjusted by the main variables described as modifiers of spirometry parameters, which are age, height, sex, disability, and a history of tobacco use. Assumptions of multicollinearity and the randomization of variances in the residuals were evaluated. Negative associations were found between spirometry parameters and the concentrations of indoor air pollutants. For FEV1/FVC and theoretical FEV1, there was a statistically significant association with the concentration of carbon monoxide (p = 0.003 and 0.019, respectively). The environmental concentrations were higher in homes where biomass was used for cooking, but these differences were statistically significant only for BC and CO (p = 0.008 and 0.03, respectively). The concentrations of carbon monoxide in rural homes were associated with alterations in respiratory function parameters.


Subject(s)
Air Pollutants , Air Pollution, Indoor , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Colombia , Cooking , Cross-Sectional Studies , Environmental Exposure , Environmental Monitoring , Humans , Particulate Matter/analysis , Rural Population , Spirometry
12.
Cells ; 9(12)2020 12 15.
Article in English | MEDLINE | ID: mdl-33333852

ABSTRACT

In highly metastatic tumors, vasculogenic mimicry (VM) involves the acquisition by tumor cells of endothelial-like traits. Poly-(ADP-ribose) polymerase (PARP) inhibitors are currently used against tumors displaying BRCA1/2-dependent deficient homologous recombination, and they may have antimetastatic activity. Long non-coding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To evaluate the impact of olaparib treatment in the context of non-coding RNA, we have analyzed the expression of lncRNA after performing unbiased whole-transcriptome profiling of human uveal melanoma cells cultured to form VM. RNAseq revealed that the non-coding transcriptomic landscape differed between olaparib-treated and non-treated cells: olaparib significantly modulated the expression of 20 lncRNAs, 11 lncRNAs being upregulated, and 9 downregulated. We subjected the data to different bioinformatics tools and analysis in public databases. We found that copy-number variation alterations in some olaparib-modulated lncRNAs had a statistically significant correlation with alterations in some key tumor suppressor genes. Furthermore, the lncRNAs that were modulated by olaparib appeared to be regulated by common transcription factors: ETS1 had high-score binding sites in the promoters of all olaparib upregulated lncRNAs, while MZF1, RHOXF1 and NR2C2 had high-score binding sites in the promoters of all olaparib downregulated lncRNAs. Finally, we predicted that olaparib-modulated lncRNAs could further regulate several transcription factors and their subsequent target genes in melanoma, suggesting that olaparib may trigger a major shift in gene expression mediated by the regulation lncRNA. Globally, olaparib changed the lncRNA expression landscape during VM affecting angiogenesis-related genes.


Subject(s)
Gene Regulatory Networks/genetics , Neovascularization, Physiologic/genetics , Phthalazines/pharmacology , Piperazines/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , RNA, Long Noncoding/genetics , Base Sequence , Cell Line, Tumor , Collagen/pharmacology , Drug Combinations , Gene Expression Regulation, Neoplastic/drug effects , Gene Regulatory Networks/drug effects , Humans , Laminin/pharmacology , Neoplasms/genetics , Neovascularization, Physiologic/drug effects , Proteoglycans/pharmacology , RNA, Long Noncoding/metabolism , Transcription Factors/metabolism , Transcription, Genetic/drug effects
13.
Cancers (Basel) ; 12(3)2020 Mar 20.
Article in English | MEDLINE | ID: mdl-32245040

ABSTRACT

Poly(ADP-ribose) polymerases (PARPs), represent a family of 17 proteins implicated in a variety of cell functions; some of them possess the enzymatic ability to synthesize and attach poly (ADP-ribose) (also known as PAR) to different protein substrates by a post-translational modification; PARPs are key components in the cellular response to stress with consequences for different physiological and pathological events, especially during neoplasia. In recent years, using PARP inhibitors as antitumor agents has raised new challenges in understanding their role in tumor biology. Notably, the function of PARPs and PAR in the dynamic of tumor microenvironment is only starting to be understood. In this review, we summarized the conclusions arising from recent studies on the interaction between PARPs, PAR and key features of tumor microenvironment such as hypoxia, autophagy, tumor initiating cells, angiogenesis and cancer-associated immune response.

14.
Front Oncol ; 9: 803, 2019.
Article in English | MEDLINE | ID: mdl-31508365

ABSTRACT

Blood vessels supply all body tissues with nutrients and oxygen, take away waste products and allow the arrival of immune cells and other cells (pericytes, smooth muscle cells) that form part of these vessels around the principal endothelial cells. Vasculogenic mimicry (VM) is a tumor blood supply system that takes place independently of angiogenesis or endothelial cells, and is associated with poor survival in cancer patients. Aberrant expression of VE-cadherin has been strongly associated with VM. Even more, VE-cadherin has constitutively high phosphorylation levels on the residue of Y658 in human malignant melanoma cells. In this review we focus on non-endothelial VE-cadherin and its post-translational modifications as a crucial component in the development of tumor VM, highlighting the signaling pathways that lead to their pseudo-endothelial and stem-like phenotype and the role of tumor microenvironment. We discuss the importance of the tumor microenvironment in VM acquisition, and describe the most recent therapeutic targets that have been proposed for the repression of VM.

15.
Cell Death Differ ; 26(2): 348-361, 2019 01.
Article in English | MEDLINE | ID: mdl-29786069

ABSTRACT

Aberrant extra-vascular expression of VE-cadherin (VEC) has been observed in metastasis associated with vasculogenic mimicry (VM); however, the ultimate reason why non-endothelial VEC favors the acquisition of this phenotype is not established. In this study, we show that human malignant melanoma cells have a constitutively high expression of phoshoVEC (pVEC) at Y658; pVEC is a target of focal adhesion kinase (FAK) and forms a complex with p120-catenin and the transcriptional repressor kaiso in the nucleus. FAK inhibition enabled kaiso to suppress the expression of its target genes and enhanced kaiso recruitment to KBS-containing promoters. Finally we have found that ablation of kaiso-repressed genes WNT11 and CCDN1 abolished VM. Thus, identification of pVEC as a component of the kaiso transcriptional complex establishes a molecular paradigm that links FAK-dependent phosphorylation of VEC as a major mechanism by which ectopical VEC expression exerts its function in VM.


Subject(s)
Antigens, CD/genetics , Antigens, CD/metabolism , Cadherins/genetics , Cadherins/metabolism , Gene Expression , Melanoma/genetics , Neovascularization, Pathologic/genetics , Skin Neoplasms/genetics , Transcription Factors/genetics , Catenins/metabolism , Cell Line, Tumor , Cyclin D1/genetics , Focal Adhesion Kinase 1/metabolism , Gene Knockout Techniques , HEK293 Cells , Human Umbilical Vein Endothelial Cells , Humans , Melanoma/pathology , Phosphorylation , Skin Neoplasms/pathology , Transduction, Genetic , Wnt Proteins/genetics , Delta Catenin
16.
Rev. Fac. Med. (Bogotá) ; 65(2): 311-319, Apr.-June 2017. tab
Article in Spanish | LILACS | ID: biblio-896721

ABSTRACT

Resumen Introducción. Los cambios en el saber y en la práctica han logrado consolidar a la fisioterapia como una profesión emergente de rápido crecimiento; sin embargo, las dinámicas del mercado y los sistemas de salud han transformado las características del recurso humano, las condiciones de trabajo y los avances y tendencias de la práctica profesional. Objetivo. Caracterizar el estado actual de la práctica profesional de la fisioterapia en el marco de organización del sistema de salud colombiano, cuyas transformaciones han impactado el conjunto de prácticas profesionales del sector salud. Materiales y métodos. Se realizó una encuesta electrónica a estudiantes de Fisioterapia de la Universidad Nacional de Colombia graduados durante el período 1980-2012 que evalúa campos y áreas de desempeño, condiciones de trabajo, autonomía profesional, valoración social y perfil de morbilidad. Resultados. La fisioterapia aparece como una profesión socialmente requerida, con campos y áreas de desempeño que se proyectan más allá del sector salud. Sin embargo, son preocupantes las condiciones de deterioro del trabajo, destacando las formas de contratación, los bajos salarios y las restricciones para la práctica profesional autónoma, en particular en el campo asistencial. Conclusiones. Es necesario garantizar condiciones de trabajo que promuevan una práctica profesional idónea y que garanticen la permanencia de los profesionales, en especial en la práctica asistencial.


Abstract Introduction: Changes in knowledge and practice have consolidated physiotherapy as an emerging fast-growing profession. However, the market dynamics and the configuration of health systems have transformed the characteristics of human resources, as well as the working conditions, advances and trends of professional practice. Objective: To characterize the current state of the professional practice of physiotherapy in the organizational framework of the Colombian health system, since its transformations have impacted the professional practices of the health sector. Materials and methods: An online survey was applied to physiotherapists graduated from Universidad Nacional de Colombia between 1980 and 2012. The survey evaluates the fields and areas of performance, working conditions, professional autonomy, social assessment and morbidity profile. Results: Physiotherapy is conceived as a profession required by society, with fields and areas of performance projected beyond the health sector. However, the deteriorating work conditions are worrying, particularly recruitment, low wages and restrictions for autonomous professional practice, especially those related to healthcare services. Conclusions: It is necessary to ensure working conditions that promote a suitable professional practice and the permanence of professionals, particularly in clinical practice.

17.
Mol Cancer ; 16(1): 65, 2017 03 21.
Article in English | MEDLINE | ID: mdl-28320399

ABSTRACT

Vasculogenic mimicry (VM) is a blood supply system independent of endothelial vessels in tumor cells from different origins. It reflects the plasticity of aggressive tumor cells that express vascular cell markers and line tumor vasculature. The presence of VM is associated with a high tumor grade, short survival, invasion and metastasis. Endothelial cells (ECs) express various members of the cadherin superfamily, in particular vascular endothelial (VE-) cadherin, which is the main adhesion receptor of endothelial adherent junctions. Aberrant extra-vascular expression of VE-cadherin has been observed in certain cancer types associated with VM. In this review we focus on non-endothelial VE-cadherin as a prominent factor involved in the acquisition of tubules-like structures by aggressive tumor cells and we summarize the specific signaling pathways, the association with trans-differentiation and stem-like phenotype and the therapeutic opportunities derived from the in-depth knowledge of the peculiarities of the biology of VE-cadherin and other key components of VM.


Subject(s)
Neoplasms/blood supply , Neoplasms/metabolism , Neovascularization, Pathologic/metabolism , Signal Transduction , Animals , Biomarkers , Cadherins/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Epithelial-Mesenchymal Transition , Humans , Hypoxia/metabolism , Neoplasms/pathology , Tumor Microenvironment
18.
Rev. Fac. Med. (Bogotá) ; 64(supl.1): 59-67, oct.-dic. 2016. tab
Article in Spanish | LILACS | ID: biblio-956815

ABSTRACT

Resumen Introducción. El estudio nacional de las condiciones de salud y trabajo de los fisioterapeutas no contaba con instrumentos diseñados y validados, coherentes con el marco analítico amplio de la relación entre salud y trabajo. Objetivo. Presentar los procesos de construcción y validación del instrumento denominado evaluación de condiciones de salud y trabajo de los fisioterapeutas en Colombia. Materiales y métodos. Se utilizó el coeficiente alfa de Cronbach para medir la relación entre las respuestas a cada variable con la magnitud de cada categoría, estableciendo mediciones fijas y consistentes con un elevado nivel de correlación. El proceso de validación se realizó en 1 711 fisioterapeutas de Colombia egresados desde el año 1980 hasta 2012. Resultados. La valoración de coherencia interna a través del alfa de Cronbach encontró cinco categorías del instrumento altamente coherentes, tres con valores mayores de 0.8: condiciones peligrosas del trabajo, organización de las tareas, satisfacción con el empleo, y dos con valoraciones superiores a 0.9: eventos en salud-enfermedad e identidad y autonomía. Discusión. El diseño y construcción del instrumento de valoración de las condiciones de salud y trabajo de los fisioterapeutas nacen de la necesidad del colectivo de fisioterapeutas para establecer líneas de base amplias sobre la relación entre el trabajo y la salud, y entender las condiciones de trabajo como elemento estructurante de la salud y enfermedad.


Abstract Introduction: The national survey on health and work conditions of physiotherapists did not have designed and validated instruments that considered the broad analytical framework of the relationship between health and work. Objective: To present construction and validation processes of the instrument known as health conditions and physical therapists work in Colombia. Materials and methods: Cronbach's alpha coefficient was used to measure the relationship between responses to each variable and the magnitude of each category, establishing fixed and consistent measurements with a high level of correlation. The validation process was carried out with 1 711 Colombian physiotherapists, graduated between 1980 and 2012. Results: The assessment of internal consistency through Cronbach's found five highly coherent categories, three values greater than 0.8 (hazardous working conditions, organization of work, job satisfaction), and two above 0.9 (events in health and disease and identity and autonomy). Discussion: The design and construction of the instrument for assessing health and work conditions of physiotherapists are generated based on the needs of physiotherapists to establish broad baselines regarding the relationship between work and health, and to understand working conditions as a structuring element of health and disease.

19.
Ciênc. rural ; 45(10): 1890-1894, Oct. 2015. tab, ilus
Article in English | LILACS | ID: lil-758036

ABSTRACT

Zein oleic acid films added with 1, 2 and 3 % (w/w) of nanocarbonate and 30 % glycerol as plasticizer, were produced and evaluated according to their structure and functional properties. Structural characteristics were analyzed by optical and scanning electron microscopy (SEM). Water solubility and mechanical properties were determined according to ASTM methods. The increase of nanocarbonate concentration increased water solubility and influenced the color and mechanical properties. Optical and SEM of film samples added with nanocarbonate, shown low amount of pores and great fat globules size.


Filmes a base de zeína e ácido oleico adicionados com 1, 2 e 3 % de nanocarbonato e 30 % de glicerol como plasticizante foram produzidos e avaliados quanto sua estrutura e propriedades funcionais. Caracteristicas estruturais foram analisadas por meio de microscopia ótica (MO) e eletrônica de varredura (MEV) e solubilidade em água e propriedades mecânicas segundo métodos da ASTM. O aumento na concentração de nanocarbonato, aumentou a solubilidade em água e influenciou na cor e propriedades mecânicas. As análises de MO e MEV do filme adicionado com nanocarbonato mostraram pouca presença de poros e glóbulos de gordura de maior tamanho quando comparado com o filme controle.

20.
Br J Nutr ; 113(6): 878-87, 2015 Mar 28.
Article in English | MEDLINE | ID: mdl-25720761

ABSTRACT

The increasing incidence of the metabolic syndrome (MetS), a combination of risk factors before the onset of CVD and type 2 diabetes, encourages studies on the role of functional food components such as long-chain n-3 PUFA as preventive agents. In the present study, we explore the effect of EPA and DHA supplementation in different proportions on spontaneously hypertensive obese (SHROB) rats, a model for the MetS in a prediabetic state with mild oxidative stress. SHROB rats were randomised into four groups (n 7), each supplemented with EPA/DHA at ratios of 1:1, 2:1 and 1:2, or soyabean oil as the control for 13 weeks. The results showed that in all the proportions tested, EPA/DHA supplementation significantly lowered total and LDL-cholesterol concentrations, compared with those of the control group. EPA/DHA supplementation at the ratios of 1:1 and 2:1 significantly decreased inflammation (C-reactive protein levels) and lowered oxidative stress (decreased excretion of urinary isoprostanes), mainly at the ratio of 1:2. The activity of antioxidant enzymes increased in erythrocytes, abdominal fat and kidneys, with magnitudes depending on the EPA:DHA ratio. PUFA mixtures from fish affected different MetS markers of CVD risk factors in SHROB rats, depending on the ratios of EPA/DHA supplementation. The activation of endogenous defence systems may be related to the reduction of inflammation and oxidative stress.


Subject(s)
Dietary Supplements , Docosahexaenoic Acids/therapeutic use , Eicosapentaenoic Acid/therapeutic use , Hypertension/prevention & control , Metabolic Syndrome/diet therapy , Obesity/complications , Prediabetic State/prevention & control , Abdominal Fat/enzymology , Abdominal Fat/immunology , Abdominal Fat/metabolism , Animals , Biomarkers/blood , Biomarkers/metabolism , Biomarkers/urine , C-Reactive Protein/analysis , Docosahexaenoic Acids/administration & dosage , Eicosapentaenoic Acid/administration & dosage , Erythrocytes/enzymology , Erythrocytes/immunology , Erythrocytes/metabolism , Female , Fish Oils/administration & dosage , Fish Oils/therapeutic use , Hypercholesterolemia/etiology , Hypercholesterolemia/prevention & control , Hypertension/etiology , Kidney/enzymology , Kidney/immunology , Kidney/metabolism , Metabolic Syndrome/complications , Metabolic Syndrome/immunology , Metabolic Syndrome/physiopathology , Oxidative Stress , Oxidoreductases/blood , Oxidoreductases/metabolism , Prediabetic State/etiology , Random Allocation , Rats, Mutant Strains
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