Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Más filtros

País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Biogerontology ; 24(4): 555-562, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37004691

RESUMEN

Aging is a topic of paramount importance in an increasingly elderly society and has been the focus of extensive research. Protein homeostasis (proteostasis) decline is a hallmark in aging and several age-related diseases, but which specific proteins and mechanisms are involved in proteostasis (de)regulation during the aging process remain largely unknown. Here, we used different text-mining tools complemented with protein-protein interaction data to address this complex topic. Analysis of the integrated protein interaction networks identified novel proteins and pathways associated to proteostasis mechanisms and aging or age-related disorders, indicating that this approach is useful to identify previously unknown links and for retrieving information of potential novel biomarkers or therapeutic targets.


Asunto(s)
Deficiencias en la Proteostasis , Proteostasis , Humanos , Anciano , Proteostasis/fisiología , Pliegue de Proteína , Envejecimiento/fisiología , Minería de Datos
2.
Gastric Cancer ; 17(3): 442-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24272205

RESUMEN

BACKGROUND: There is still no widely accepted molecular marker available to distinguish between gastric high-grade intraepithelial neoplasia (HG-IEN) and invasive early gastric cancer (EGC). METHODS: HG-IEN and EGC lesions coexisting in the same patient were manually microdissected from a series of 15 gastrectomies for EGC; 40 ng DNA was used for multiplex PCR amplification using the Ion AmpliSeq Cancer Panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes. RESULTS: Of the 15 EGCs, 12 presented at least one somatic mutation among the 50 investigated genes, and 6 of these showed multiple driver gene somatic mutations. TP53 mutations were observed in 9 cases; APC mutations were identified in 3 cases; and ATM and STK11 were mutated in 2 cases. Seven HG-IEN lesions shared an identical mutational profile with the EGC from the same patient; 13 mutations observed in APC, ATM, FGFR3, PIK3CA, RB1, STK11, and TP53 genes were shared by both HG-IEN and ECG lesions. CDKN2A, IDH2, MET, and RET mutations were observed only in EGC. TP53 deregulation was further investigated in an independent series of 75 biopsies corresponding to all the phenotypic lesions occurring in the EGC carcinogenetic cascade. p53 nuclear immunoreaction progressively increased along with the dedifferentiation of the lesions (P < 0.001). Overall, 18 of 20 p53-positive lesions showed a TP53 mutated gene. DISCUSSION: Our results support the molecular similarity between HG-IEN and EGC and suggest a relevant role for TP53 in the progression to the invasive phenotype and the use of immunohistochemistry as a surrogate to detect TP53 gene mutations.


Asunto(s)
Carcinoma in Situ/patología , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Anciano , Biopsia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/genética , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mutación , Invasividad Neoplásica , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética
3.
JMIR Med Inform ; 12: e49646, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654577

RESUMEN

Background: The SARS-CoV-2 pandemic has demonstrated once again that rapid collaborative research is essential for the future of biomedicine. Large research networks are needed to collect, share, and reuse data and biosamples to generate collaborative evidence. However, setting up such networks is often complex and time-consuming, as common tools and policies are needed to ensure interoperability and the required flows of data and samples, especially for handling personal data and the associated data protection issues. In biomedical research, pseudonymization detaches directly identifying details from biomedical data and biosamples and connects them using secure identifiers, the so-called pseudonyms. This protects privacy by design but allows the necessary linkage and reidentification. Objective: Although pseudonymization is used in almost every biomedical study, there are currently no pseudonymization tools that can be rapidly deployed across many institutions. Moreover, using centralized services is often not possible, for example, when data are reused and consent for this type of data processing is lacking. We present the ORCHESTRA Pseudonymization Tool (OPT), developed under the umbrella of the ORCHESTRA consortium, which faced exactly these challenges when it came to rapidly establishing a large-scale research network in the context of the rapid pandemic response in Europe. Methods: To overcome challenges caused by the heterogeneity of IT infrastructures across institutions, the OPT was developed based on programmable runtime environments available at practically every institution: office suites. The software is highly configurable and provides many features, from subject and biosample registration to record linkage and the printing of machine-readable codes for labeling biosample tubes. Special care has been taken to ensure that the algorithms implemented are efficient so that the OPT can be used to pseudonymize large data sets, which we demonstrate through a comprehensive evaluation. Results: The OPT is available for Microsoft Office and LibreOffice, so it can be deployed on Windows, Linux, and MacOS. It provides multiuser support and is configurable to meet the needs of different types of research projects. Within the ORCHESTRA research network, the OPT has been successfully deployed at 13 institutions in 11 countries in Europe and beyond. As of June 2023, the software manages data about more than 30,000 subjects and 15,000 biosamples. Over 10,000 labels have been printed. The results of our experimental evaluation show that the OPT offers practical response times for all major functionalities, pseudonymizing 100,000 subjects in 10 seconds using Microsoft Excel and in 54 seconds using LibreOffice. Conclusions: Innovative solutions are needed to make the process of establishing large research networks more efficient. The OPT, which leverages the runtime environment of common office suites, can be used to rapidly deploy pseudonymization and biosample management capabilities across research networks. The tool is highly configurable and available as open-source software.

4.
Front Public Health ; 12: 1303786, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38450149

RESUMEN

Introduction: Multisectoral action is a central component of the global response to the rising prevalence of non-communicable diseases (NCDs). In this paper we aimed to unpack the definition of multisectoral action and provide an overview of the historical context, challenges, and recommendations alongside three country case studies: salt reduction in the UK, tobacco legislation in Nigeria, and regulation of edible oils in Iran. Methods: We used an iterative review process to select three country case studies from a list of 20 potential cases previously identified by WHO. At our third round of review we unanimously agreed to focus on salt reduction in the UK, tobacco regulation in Nigeria, and edible oil regulation in Iran as these represented rich cases on diverse risk factors from three different world regions that we felt offered important lessons. We conducted literature reviews to identify further data for each case study. Results: Across the three studies a number of important themes emerged. We found that multisectoral approaches demand the often difficult reconciliation of competing and conflicting values and priorities. Across our three chosen cases, commercial interests and free trade agreements were the most common obstacles to successful multisectoral strategies. We found that early consultative stakeholder engagement and strong political and bureaucratic leadership were necessary for success. Discussion: The complex multi-rooted nature of NCDs requires a multisectoral approach, but the inevitable conflicts that this entails requires careful navigation.


Asunto(s)
Enfermedades no Transmisibles , Liderazgo , Enfermedades no Transmisibles/prevención & control , Cloruro de Sodio Dietético , Productos de Tabaco/legislación & jurisprudencia
5.
Life Sci ; 328: 121814, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37236602

RESUMEN

Excitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.g. ischemic stroke). Multiple mechanisms and pathways lead to excitotoxic cell damage including pro-death signaling cascade events downstream of glutamate receptors, calcium (Ca2+) overload, oxidative stress, mitochondrial impairment, excessive glutamate in the synaptic cleft as well as altered energy metabolism. Here, we review the current knowledge on the molecular mechanisms that underlie excitotoxicity, emphasizing the role of Nicotinamide Adenine Dinucleotide (NAD) metabolism. We also discuss novel and promising therapeutic strategies to treat excitotoxicity, highlighting recent clinical trials. Finally, we will shed light on the ongoing search for stroke biomarkers, an exciting and promising field of research, which may improve stroke diagnosis, prognosis and allow better treatment options.


Asunto(s)
Ácido Glutámico , Accidente Cerebrovascular , Animales , Humanos , Ácido Glutámico/metabolismo , Receptores de Glutamato/metabolismo , Isquemia , Muerte Celular/fisiología , Mamíferos/metabolismo
6.
Biomedicines ; 11(5)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37238993

RESUMEN

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.

7.
Neurochem Int ; 159: 105402, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35843422

RESUMEN

BACKGROUND: Nicotinamide adenine dinucleotide (NAD) metabolism is involved in redox and non-redox reactions that regulate several processes including differentiation of cells of different origins. Here, the role of NAD metabolism in neuronal differentiation, which remains elusive so far, was investigated. MATERIAL AND METHODS: A protein-protein interaction network between neurotrophin signaling and NAD metabolic pathways was built. Expression of NAD biosynthetic enzymes in SH-SY5Y cells during retinoic acid (RA)/brain derived neurotrophic factor (BDNF) differentiation, was evaluated. The effects of NAD biosynthetic enzymes QPRT and NAPRT inhibition in neurite outgrowth, cell viability, NAD availability and histone deacetylase (HDAC) activity, were analyzed in RA- and BDNF-differentiated cells. RESULTS: Bioinformatics analysis revealed the interaction between NAD biosynthetic enzyme NMNAT1 and NTRK2, a receptor activated by RA/BDNF sequential treatment. Differences were found in the expression of NAD biosynthetic enzymes during neuronal differentiation, namely, increased QPRT gene expression along the course of RA/BDNF treatment and NAPRT protein expression after a 5-day treatment with RA. QPRT inhibition in BDNF-differentiated SH-SY5Y cells resulted in less neuritic length per cell, decreased expression of the neuronal marker ß-III Tubulin and also decreased NAD+ levels and HDAC activity. NAPRT inhibition had no effect in neuritic length per cell, NAD+ levels and HDAC activity. Of note, NAD supplementation along with RA, but not with BDNF, resulted in considerable cell death. CONCLUSIONS: Taken together, our results show the involvement of NAD metabolism in neuronal differentiation, specifically, the importance of QPRT-mediated NAD biosynthesis in BDNF-associated SH-SY5Y differentiation and suggest additional roles for NAPRT beyond NAD production in RA-differentiated cells.


Asunto(s)
Neuroblastoma , Nicotinamida-Nucleótido Adenililtransferasa , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Diferenciación Celular , Línea Celular Tumoral , Humanos , NAD/metabolismo , Tretinoina/metabolismo , Tretinoina/farmacología , Tubulina (Proteína)/metabolismo
8.
Am J Ophthalmol Case Rep ; 27: 101653, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35845750

RESUMEN

Purpose: To describe the presence of bacillary layer detachment (BALAD) in serpiginous-like choroiditis (SLC) in presumed intraocular tuberculosis. Observations: Clinical and multimodal imaging including fundus photography, fundus autofluorescence, and spectral domain and enhanced-deep imaging optical coherence tomography (OCT) of two cases of SLC in presumed intraocular tuberculosis. Two patients (26 and 38-year-old woman) presented with unilateral, decreased vision of acute onset. They were diagnosed with SLC in presumed intraocular tuberculosis, and OCT revealed splitting of the ellipsoid zone, resembling BALAD. All two patients showed complete resolution after treatment with antitubercular therapy (ATT). Conclusions and Importance: BALAD appears in the acute stage of SLC in presumed intraocular tuberculosis and resolves rapidly at the beginning of ATT.

9.
Ophthalmic Surg Lasers Imaging Retina ; 50(11): e300-e310, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31755982

RESUMEN

BACKGROUND AND OBJECTIVE: Diabetic macular edema (DME) is a leading cause of vision loss worldwide. The object of this study is to compare global differences of baseline characteristics of patients undergoing initiation of anti-vascular endothelial growth factor (VEGF) therapy for DME. PATIENTS AND METHODS: This multicenter, cross-sectional study included diabetic patients with foveal-involving retinal edema secondary to DME as documented by fundus exam and optical coherence tomography who were undergoing initiation of intravitreal anti-VEGF drugs. Variables were collected to find possible risk factors and to create an epidemiological profile of DME patients undergoing initiation of anti-VEGF agents. RESULTS: Nine hundred two patients were selected. Mean age was 62.4 (±11) years, 49.7% were Caucasians, 57.6% were male, and 96% had type two diabetes with an average disease duration of 181.7 months ± 113 months. Of the patients included, 74.7% suffered from hypertension, 26.6% from cardiovascular disease, 12.1% from cerebrovascular disease, 12.8% from peripheral vascular disease, and 12.8% from renal insufficiency. Best-corrected visual acuity (BCVA) was 65 (±20) Early Treatment Diabetic Retinopathy Study letters, central subfield thickness was 364 (±162) µm, cube volume 11.1 ± 3.1 mm3, cube average thickness 328.8 µm ± 61 µm, and 63.9% had nonproliferative diabetic retinopathy. Comparison between U.S. versus international patients, and patients with BCVA 70 letters or less versus more than 70 letters were performed, significant differences were acknowledged, and risk factors were recognized. CONCLUSION: There were key differences in the epidemiologic profile between patients presenting with DME in the U.S. and internationally. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e300-e310.].


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética , Edema Macular , Ranibizumab/uso terapéutico , Anciano , Estudios Transversales , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Retinopatía Diabética/patología , Retinopatía Diabética/fisiopatología , Femenino , Humanos , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Edema Macular/patología , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Retina/patología , Factores de Riesgo , Agudeza Visual/fisiología
10.
Mol Oncol ; 11(8): 895-912, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28156048

RESUMEN

Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short-chain O-glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST), which are generally associated with poor prognosis. We have also explored the nature of T antigen sialylation, namely the sialyl-3-T(S3T) and sialyl-6-T(S6T) sialoforms, based on combinations of enzymatic treatments. We observed a predominance of sialoglycans over neutral glycoforms (Tn and T antigens) in bladder tumours. In particular, the STn antigen was associated with high-grade disease and muscle invasion, in accordance with our previous observations. The S3T and S6T antigens were detected for the first time in bladder tumours, but not in healthy urothelia, highlighting their cancer-specific nature. These glycans were also overexpressed in advanced lesions, especially in cases showing muscle invasion. Glycoproteomic analyses of advanced bladder tumours based on enzymatic treatments, Vicia villosa lectin-affinity chromatography enrichment and nanoLC-ESI-MS/MS analysis resulted in the identification of several key cancer-associated glycoproteins (MUC16, CD44, integrins) carrying altered glycosylation. Of particular interest were MUC16 STn+ -glycoforms, characteristic of ovarian cancers, which were found in a subset of advanced-stage bladder tumours facing the worst prognosis. In summary, significant alterations in the O-glycome and O-glycoproteome of bladder tumours hold promise for the development of novel noninvasive diagnostic tools and targeted therapeutics. Furthermore, abnormal MUC16 glycoforms hold potential as surrogate biomarkers of poor prognosis and unique molecular signatures for designing highly specific targeted therapeutics.


Asunto(s)
Glicoproteínas/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Proteínas de Neoplasias/metabolismo , Proteómica , Neoplasias de la Vejiga Urinaria/metabolismo , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Vejiga Urinaria/patología
11.
Mar Pollut Bull ; 99(1-2): 301-4, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26231069

RESUMEN

Benthic marine litter along the Portuguese coast, was recorded in 14 trips on stern trawlers covering a distance of 2117 km and an area of 56.2 km(2), average depth range 90-349 m. 2034 items of marine litter were registered, 76% were plastics and 38.6% were originated from fishing related activities. Plastic was present in all the trawls and had the highest average density of all litter categories, 50 items km(-2). The highest density of marine litter (178.9 ± 64.0 items km(-2)) was found in the proximity of the Tagus river mouth, probably related to the high population density in the Lisbon metropolitan area. This study highlights the need to raise fishermen awareness for the adoption of good environmental practices that will contribute to the reduction of marine litter.


Asunto(s)
Monitoreo del Ambiente , Residuos/análisis , Contaminantes del Agua/análisis , Animales , Explotaciones Pesqueras , Plásticos/análisis , Portugal , Ríos
12.
Mar Pollut Bull ; 101(1): 119-126, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26608506

RESUMEN

The digestive tract contents of 263 individuals from 26 species of commercial fish were examined for microplastics. These were found in 17 species, corresponding to 19.8% of the fish of which 32.7% had ingested more than one microplastic. Of all the fish that ingested microplastics, 63.5% was benthic and 36.5% pelagic species. A total of 73 microplastics were recorded, 48 (65.8%) being fibres and 25 (34.2%) being fragments. Polymers were polypropylene, polyethylene, alkyd resin, rayon, polyester, nylon and acrylic. The mean of ingested microplastics was 0.27 ± 0.63 per fish, (n=263). Pelagic fish ingested more particles and benthic fish ingested more fibres, but no significant differences were found. Fish with the highest number of microplastics were from the mouth of the Tagus river. Scomber japonicus registered the highest mean of ingested microplastics, suggesting its potential as indicator species to monitor and investigate trends in ingested litter, in the MSFD marine regions.


Asunto(s)
Exposición a Riesgos Ambientales/análisis , Peces , Contenido Digestivo , Plásticos , Contaminantes Químicos del Agua/análisis , Animales , Celulosa/análisis , Ecotoxicología/métodos , Monitoreo del Ambiente/métodos , Estuarios , Contenido Digestivo/química , Tracto Gastrointestinal/química , Plásticos/análisis , Polietileno/análisis , Polipropilenos/análisis , Portugal , Especificidad de la Especie
13.
Glob Public Health ; 10(9): 1017-31, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25646899

RESUMEN

Within the World Health Organization-International Atomic Energy Agency (WHO-IAEA) collaboration for delivery of technical assistance to its Member States, the National Cancer Control Programme/Plan (NCCP) Core Capacity Self-Assessment Tool has been used to obtain a simple and quick qualitative overview of national cancer control planning and on-going activities. The NCCP tool was applied in 50 Member States, which were classified as low- and middle-income countries in 2012. Results show that half of these countries reported having officially endorsed an NCCP and 42% were in the process of preparing or updating one. Overall, the most relevant cancer control interventions reported to be partially developed or well established in most countries were related to the cancer prevention, early detection of cervical and breast cancers, as well as diagnosis and treatment of curable cancers. Contrarily, patient's rehabilitation, psychosocial support, human papilloma virus vaccination, breast cancer screening with mammography and control of occupational carcinogens were noted as being in early development phases. The availability of crucial resources to support interventions was perceived to be the highest in upper middle-income countries. These findings highlight specific areas where WHO, IAEA and partners could strengthen collaboration with countries to leverage on-going interventions and improve availability of resources.


Asunto(s)
Creación de Capacidad/organización & administración , Implementación de Plan de Salud/estadística & datos numéricos , Neoplasias/prevención & control , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Creación de Capacidad/métodos , Creación de Capacidad/estadística & datos numéricos , Países en Desarrollo/economía , Países en Desarrollo/estadística & datos numéricos , Detección Precoz del Cáncer , Femenino , Encuestas de Atención de la Salud , Implementación de Plan de Salud/métodos , Implementación de Plan de Salud/organización & administración , Humanos , Agencias Internacionales , Cooperación Internacional , Neoplasias/diagnóstico , Neoplasias/epidemiología , Investigación Cualitativa , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Organización Mundial de la Salud
14.
PLoS One ; 10(11): e0141253, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26569621

RESUMEN

Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment. Altered protein glycosylation translated by the expression of the sialyl-Tn antigen (STn) and its precursor Tn as well as the activation of the PI3K/Akt/mTOR pathway are cancer-associated events that may hold potential for patient stratification and guided therapy. Therefore, a retrospective design, 96 bladder tumours of different stages (Ta, T1-T4) was screened for STn and phosphorylated forms of Akt (pAkt), mTOR (pmTOR), S6 (pS6) and PTEN, related with the activation of the PI3K/Akt/mTOR pathway. In our series the expression of Tn was residual and was not linked to stage or outcome, while STn was statically higher in MIBC when compared to non-muscle invasive tumours (p = 0.001) and associated decreased cancer-specific survival (log rank p = 0.024). Conversely, PI3K/Akt/mTOR pathway intermediates showed an equal distribution between non-muscle invasive bladder cancer (NMIBC) and MIBC and did not associate with cancer-specif survival (CSS) in any of these groups. However, the overexpression of pAKT, pmTOR and/or pS6 allowed discriminating STn-positive advanced stage bladder tumours facing worst CSS (p = 0.027). Furthermore, multivariate Cox regression analysis revealed that overexpression of PI3K/Akt/mTOR pathway proteins in STn+ MIBC was independently associated with approximately 6-fold risk of death by cancer (p = 0.039). Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin). This decreased the number of invasive lesions and, concomitantly, the expression of STn and also pS6, the downstream effector of the PI3K/Akt/mTOR pathway. In conclusion, STn was found to be marker of poor prognosis in bladder cancer and, in combination with PI3K/Akt/mTOR pathway evaluation, holds potential to improve the stratification of stage disease. Animal experiments suggest that mTOR pathway inhibition could be a potential therapeutic approach for this specific subtype of MIBC.


Asunto(s)
Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Glicosilación , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/mortalidad
15.
Vet Parasitol ; 200(3-4): 295-8, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24433853

RESUMEN

The present study was conducted to evaluate the prevalence of gastrointestinal parasites in dogs with no clinical signs (n=175; group H) and in dogs with gastrointestinal disease (n=193; group D) that were admitted to a veterinary hospital. In group H, the overall prevalence of intestinal parasites (i.e. the presence of at least one species) was 20.6%. Cystoisospora canis was the most prevalent protozoon (8.0%) followed by Giardia spp. (7.4%); Toxocara canis (5.1%) was the most frequent helminth, followed by Trichuris vulpis (1.1%) and Toxascaris leonina (0.6%). Among group H, age ≤ 6 months was found to be a risk factor for infection with C. canis and with at least one agent (odds ratio [OR]=3.4). In group D parasites were found in 33.7% of the dogs, with Giardia spp. (15.5%) being the most prevalent species, followed by C. canis (13.5%), T. canis (7.8%), T. vulpis (2.6%) and T. leonina (0.5%). In group D dogs, age ≤ 6 months was a risk factor for infection with Giardia spp. (OR=3.2), with C. canis (OR=32.7) and with at least one agent (OR=7.2). This study reveals a remarkable number of dogs infected but with no clinical signs.


Asunto(s)
Enfermedades de los Perros/epidemiología , Parasitosis Intestinales/veterinaria , Animales , Enfermedades de los Perros/parasitología , Perros , Eucariontes/fisiología , Femenino , Helmintos/fisiología , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Masculino , Portugal , Prevalencia
16.
Virchows Arch ; 465(1): 73-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24828033

RESUMEN

Sporadic medullary thyroid carcinoma (MTC) harbors RET gene somatic mutations in up to 50 % of cases, and RAS family gene mutations occur in about 10 %. A timely and comprehensive characterization of molecular alterations is needed to improve MTC diagnostic stratification and design-tailored therapeutic approaches. Twenty surgically resected sporadic MTCs, previously analyzed for RET mutations by Sanger sequencing using DNA from formalin-fixed paraffin-embedded samples, were investigated for intragenic mutations in 50 cancer-associated genes applying a multigene Ion AmpliSeq next-generation sequencing (NGS) technology. Thirteen (65 %) MTCs harbored a RET mutation; 10 were detected at both Sanger and NGS sequencing, while 3 undetected by Sanger were revealed by NGS. One of the 13 RET-mutated cases also showed an F354L germline mutation in STK11. Of the seven RET wild-type MTCs, four cases (57.1 %) harbored a RAS mutation: three in HRAS (all Q61R) and one in KRAS (G12R). The three remaining MTCs (15 %) resulted as wild-type for all the 50 cancer-related genes. Follow-up was available in all but one RET-mutated case. At the end of follow-up, 7 of 12 (58 %) RET-mutated patients had relapsed, while the 4 RAS-mutated MTC patients were disease-free. Two of the three patients with MTC wild-type for all 50 genes relapsed during the follow-up period. Detection of mutations by NGS has the potential to improve the diagnostic stratification of sporadic MTC.


Asunto(s)
Carcinoma Medular/genética , Neoplasias de la Tiroides/genética , Quinasas de la Proteína-Quinasa Activada por el AMP , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Neuroendocrino , Niño , Análisis Mutacional de ADN/métodos , Femenino , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-ret/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos
17.
Int J Pharm ; 422(1-2): 125-31, 2012 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-22063301

RESUMEN

In this study, indomethacin-loaded thermally oxidized mesoporous silicon microparticles (TOPSi-IMC) were formulated into tablets with excipients in order to improve the dissolution and permeability properties of the poorly soluble drug. Formulations of TOPSi-IMC particles and excipients were prepared at different TOPSi-IMC particle ratios (25, 30 and 35%). The formulations were compressed by direct compression technique with a single punch tablet machine. For comparison, a formulation containing the bulk IMC (indomethacin) and the same excipients without thermally oxidized mesoporous silicon microparticles particles (TOPSi) was prepared and compressed into tablets. The TOPSi-IMC tablets were characterised according to weight, thickness, crushing strength, disintegration time and dissolution rate. The results of this study show that TOPSi-IMC particles can be compressed to a conventional tablet. The release rate of the drug and its permeation across intestinal cells model (Caco-2) from TOPSi-IMC tablets was improved compared to the bulk IMC tablets. The dissolution rate and permeability of IMC from the tablets decreased with increasing ratio of the TOPSi-IMC particles in the formulation. The phenomenon is, presumably, a result of the loss of unique pore structure of the particles due to deformation of the particles under the compression load.


Asunto(s)
Antiinflamatorios no Esteroideos/química , Portadores de Fármacos , Indometacina/química , Silicio/química , Antiinflamatorios no Esteroideos/metabolismo , Células CACO-2 , Química Farmacéutica , Fuerza Compresiva , Composición de Medicamentos , Excipientes/química , Humanos , Indometacina/metabolismo , Absorción Intestinal , Mucosa Intestinal/metabolismo , Cinética , Oxidación-Reducción , Tamaño de la Partícula , Permeabilidad , Porosidad , Solubilidad , Comprimidos , Tecnología Farmacéutica/métodos , Temperatura
18.
Rev. méd. Minas Gerais ; 19(1): 51-57, jan.-mar. 2009.
Artículo en Portugués | LILACS | ID: lil-546396

RESUMEN

Esta revisão discorre sobre uma das principais doenças que acometem o recém-nascido prematuro com peso inferior a 1.500 g, ocasionando alta morbidade e mortalidade no período neonatal. São relatados os principais fatores de risco, clínica, exames complementares e o tratamento atual.


Asunto(s)
Humanos , Recién Nacido , Enterocolitis Necrotizante , Recien Nacido Prematuro , Recién Nacido de Bajo Peso , Perforación Intestinal , Neumatosis Cistoide Intestinal
19.
HU rev ; 35(4): 324-327, out.-dez. 2009. tab
Artículo en Portugués | LILACS | ID: lil-543926

RESUMEN

A infecção congênita pelo Toxoplasma gondii é uma condição potencialmente grave, prevenível e tratável. Será descrito um caso de óbito perinatal, ocorrido por infecção congênita pelo agente T. gondii, cuja sintomatologia principal foi uma grave colestase neonatal em um paciente nascido na Maternidade de um Hospital Público, na cidade de Juiz de Fora/MG. A mãe não realizou pré-natal. O T. gondii foi identificado por anatomia patológica (macroscopia e microscopia), com presença de cistos de T. gondii no cérebro, coração, pulmões, fígado, e baço, com intenso comprometimento intra-hepático. É essencial garantir que todas as mulheres tenham acesso ao pré-natal e que reconheçam a necessidade de fazê-lo o mais rápido possível e adequadamente. Além disso, é imprescindível que os profissionais da área de saúde estejam atentos para o reconhecimento precoce de possíveis casos e a instituição do tratamento adequado, reduzindo a mortalidade e, se possível, minimizandoa ocorrência de sequelas.


Toxoplasma gondii congenital infection is potentially serious, although preventable and treatable. We report a case of perinatal death due to a congenital infection with T. gondii, in which the dominant feature was severe neonatal colestasis. The baby, born to a mother who did not attend antenatal consultations, was delivered in a public maternity in the city of Juiz de Fora, Minas Gerais, Brazil. T. gondii was identified on pathology (gross anatomy and microscopy), with identification of cysts in the brain, heart, lungs, liver and spleen, with intense intra-hepatic involvement. It is essential to guarantee universal access to antenatal care and empower women to attend it early and adequately. Furthermore, health professionalsshould be attentive to early recognition of possible cases and treatment initiation, so that mortality and sequelae are reduced.


Asunto(s)
Toxoplasmosis , Colestasis , Toxoplasma , Toxoplasmosis Congénita
20.
Coimbra; s.n; mar. 2013. 98 p. ilus, tab, graf.
Tesis en Portugués | BDENF - enfermagem (Brasil) | ID: biblio-1425245

RESUMEN

As instituições de saúde são organizações de estruturação complexa, dinâmica e em constante mudança. Neste contexto, são necessários profissionais de saúde detentores de competências de liderança, capazes de influenciar os comportamentos dos subordinados no sentido da consecução dos objectivos organizacionais, e, simultaneamente, promotores da satisfação. Este estudo foi realizado em contexto hospitalar e teve como principal objectivo verificar a relação do desempenho dos papéis de liderança e a satisfação com a supervisão. Foi realizado um estudo quantitativo, descritivo, correlacional e transversal numa amostra constituída por 79 enfermeiros. Na colheita de dados foi aplicado um questionário, constituído por dados sociodemográficos, Escala de Liderança e Escala de Satisfação com a Supervisão. Os resultados apontam para um reconhecimento do desempenho de todos os papéis de liderança, configurando-se, um pendor para o controlo. Os papéis de liderança mais reconhecidos foram os de director e produtor, apontando a liderança para o modelo dos objectivos racionais, indiciando uma maior preocupação dos enfermeiros chefes com o planeamento, definição de metas, produtividade e eficiência. Os enfermeiros encontram-se globalmente satisfeitos com a supervisão, verificando-se diferenças estatisticamente significativas entre a satisfação com a supervisão e a prática do horário fixo. Verificou-se, também, uma associação positiva significativa para todos os papéis de liderança, sendo, os papéis de facilitador e mentor, os que apresentam correlações mais fortes. A investigação revelou que o líder que desempenha todos os papéis de liderança, para além de adquirir níveis de performance mais elevados, também, aumenta o nível de satisfação com a supervisão dos enfermeiros que lidera.


Asunto(s)
Organización y Administración , Empatía , Satisfacción en el Trabajo , Liderazgo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA