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1.
Sci Rep ; 8(1): 9172, 2018 06 15.
Article in English | MEDLINE | ID: mdl-29907864

ABSTRACT

Non Muscle Invasive Bladder Cancer (NMIBC) is among the most frequent malignant cancers worldwide. NMIBC is treated by transurethral resection of the bladder tumor (TURBT) and intravesical therapies, and has the highest recurrence rate among solid tumors. It requires a lifelong patient monitoring based on repeated cystoscopy and urinary cytology, both having drawbacks that include lack of sensitivity and specificity, invasiveness and care costs. We conducted an investigative clinical study to examine changes in the urinary metabolome of NMBIC patients before and after TURBT, as well during the subsequent surveillance period. Adjusting by prior probability of recurrence per risk, discriminant analysis of UPLC-MS metabolic profiles, displayed negative predictive values for low, low-intermediate, high-intermediate and high risk patient groups of 96.5%, 94.0%, 92.9% and 76.1% respectively. Detailed analysis of the metabolome revealed several candidate metabolites and perturbed phenylalanine, arginine, proline and tryptophan metabolisms as putative biomarkers. A pilot retrospective analysis of longitudinal trajectories of a BC metabolic biomarkers during post TURBT surveillance was carried out and the results give strong support for the clinical use of metabolomic profiling in assessing NMIBC recurrence.


Subject(s)
Biomarkers, Tumor/urine , Metabolome , Metabolomics , Urinary Bladder Neoplasms , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/urine
2.
Sci Rep ; 7: 45517, 2017 04 12.
Article in English | MEDLINE | ID: mdl-28401960

ABSTRACT

Despite dedicated research has been carried out to adequately map the distribution of the sperm whale in the Mediterranean Sea, unlike other regions of the world, the species population status is still presently uncertain. The analysis of two years of continuous acoustic data provided by the ANTARES neutrino telescope revealed the year-round presence of sperm whales in the Ligurian Sea, probably associated with the availability of cephalopods in the region. The presence of the Ligurian Sea sperm whales was demonstrated through the real-time analysis of audio data streamed from a cabled-to-shore deep-sea observatory that allowed the hourly tracking of their long-range echolocation behaviour on the Internet. Interestingly, the same acoustic analysis indicated that the occurrence of surface shipping noise would apparently not condition the foraging behaviour of the sperm whale in the area, since shipping noise was almost always present when sperm whales were acoustically detected. The continuous presence of the sperm whale in the region confirms the ecological value of the Ligurian sea and the importance of ANTARES to help monitoring its ecosystems.

3.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 35(6): 373-378, nov.-dic. 2016. tab, ilus, graf
Article in Spanish | IBECS | ID: ibc-157473

ABSTRACT

Objetivos. Evaluar el uso de la 4D PET/TC para capturar el movimiento respiratorio en comparación con la «slow»-TC (TCs), en el procedimiento de planificación de radioterapia. Material y métodos. Se ha incluido a 25 pacientes diagnosticados de estadio inicial de cáncer de pulmón de célula no pequeña (NSCLC) médicamente inoperable. A cada paciente se le realizó una TCs (4 s/corte) y una 4D PET/TC. La idoneidad de cada técnica en la captura del movimiento respiratorio fue evaluada comparando el volumen definido por cada una de ellas: internal target volumen (ITV) 4D y el ITVslow, con relación a la suma de los volúmenes de la 4D PET/TC y la TCs (ITVsuma). La máxima diferencia entre el volumen definido por cada técnica respecto al volumen suma fue evaluada en una proyección antero-posterior y otra lateral. Resultados. Los volúmenes generados con 4D PET/TC consiguen una definición más precisa del ITV que los volúmenes obtenidos con TCs (ITV4D/ITVsuma 78% vs. ITVslow/ITVsuma 63%). En general, los volúmenes de la 4D PET/TC son de mayor tamaño (19,9 vs. 16,3 cc). El ITV4D muestra menor diferencia con el ITVsuma en los ejes cráneo-caudal y antero-posterior respecto al ITVslow y capta el movimiento de forma más exacta. La máxima diferencia observada es de 0,36mm en la 4D PET/TC y de 0,57mm en la TCs en el eje antero-posterior. Conclusiones. La planificación con 4D PET/TC en comparación con TCs permite cuantificar el movimiento respiratorio del tumor y mejorar la planificación de radioterapia en estadios iniciales de NSCLC (AU)


Objectives. To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow»-CT (CTs) in the radiotherapy planning process. Material and methods. A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. Results. The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. Conclusion. Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer (AU)


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung , Carcinoma, Non-Small-Cell Lung/radiotherapy , Positron-Emission Tomography/instrumentation , Positron-Emission Tomography/methods , Positron-Emission Tomography , Nuclear Medicine/methods , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/analysis , Radiopharmaceuticals/therapeutic use
4.
Rev. esp. med. nucl. imagen mol. (Ed. impr.) ; 35(5): 287-291, sept.-oct. 2016. tab, ilus, graf
Article in English | IBECS | ID: ibc-155011

ABSTRACT

Background. The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. Materials and methods. Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc99m-labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. Results. Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. Conclusions. This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation (AU)


Objetivo. Tras una resección quirúrgica completa, la recidiva local del cancer de páncreas es de aproximadamente el 30%. La linfadenectomía extendida podría mejorar la supervivencia pero implica una morbilidad grave, por lo que una adecuada selección de los pacientes seria fundamental. Presentamos una nueva técnica de determinación del ganglio centinela (GC) en el cáncer de páncreas mediante el uso de SPECT/TC y sonda gamma. Materiales y Métodos. Siete pacientes con cáncer de páncreas estadío cT2N0M0 fueron incluidos entre 2009 y 2012 en este estudio prospectivo. El día antes de la cirugía se realizó una ecoendoscopia con inyección intratumoral de un nanocoloide marcado con Tc99m y dos horas más tarde se obtuvieron imágenes planares y de SPECT-TC. Intraoperatoriamente se realizó asimismo un rastreo con sonda gamma para detectar el GC. Resultados. La administración del radiotrazador fue posible en todos los pacientes. La linfogammagrafía detectó ganglios interaortocavos en 2 pacientes, ganglios en el ligamento hepatoduodenal en 1 paciente, inyección intravascular en 3 pacientes, tránsito intestinal en 5 pacientes y visualizó el conducto pancreático principal en 1 paciente. Debido a la progresión local, la resección quirúrgica pudo ser completada únicamente en 4 pacientes. La detección intraoperatoria del GC se completo en 2 pacientes, ambos con resultado negativo. Sólo en uno de estos pacientes el resultado pudo confirmarse con el estudio anatomopatológico definitivo. Conclusiones. Este nuevo método de detección del GC en cáncer de páncreas es viable pero complejo. Nuestros resultados preliminares con 7 pacientes no permiten una validación clínica (AU)


Subject(s)
Humans , Male , Female , Sentinel Lymph Node Biopsy/methods , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms , Lymphoscintigraphy/methods , Lymphoscintigraphy , Tomography, Emission-Computed, Single-Photon/methods , Tomography, Emission-Computed, Single-Photon , Molecular Probe Techniques , Pancreas/pathology , Pancreas , Prospecting Probe , Technetium Tc 99m Medronate/analysis , Endoscopy/methods , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy , Intraoperative Complications/surgery
5.
Rev Esp Med Nucl Imagen Mol ; 35(6): 373-378, 2016.
Article in English, Spanish | MEDLINE | ID: mdl-27106507

ABSTRACT

OBJECTIVES: To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow¼-CT (CTs) in the radiotherapy planning process. MATERIAL AND METHODS: A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. RESULTS: The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. CONCLUSION: Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/radiotherapy , Four-Dimensional Computed Tomography , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Positron Emission Tomography Computed Tomography , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Four-Dimensional Computed Tomography/methods , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Radiotherapy Planning, Computer-Assisted/methods , Respiration , Time Factors
6.
J Struct Biol ; 195(1): 93-9, 2016 07.
Article in English | MEDLINE | ID: mdl-27108186

ABSTRACT

In the past few years, 3D electron microscopy (3DEM) has undergone a revolution in instrumentation and methodology. One of the central players in this wide-reaching change is the continuous development of image processing software. Here we present Scipion, a software framework for integrating several 3DEM software packages through a workflow-based approach. Scipion allows the execution of reusable, standardized, traceable and reproducible image-processing protocols. These protocols incorporate tools from different programs while providing full interoperability among them. Scipion is an open-source project that can be downloaded from http://scipion.cnb.csic.es.


Subject(s)
Algorithms , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/instrumentation , Microscopy, Electron/methods , Imaging, Three-Dimensional/methods , Reproducibility of Results , Workflow
7.
Arch Toxicol ; 90(9): 2215-2229, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26525393

ABSTRACT

The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.


Subject(s)
Carcinogens/toxicity , Computational Biology , Gene Expression Profiling , Kidney Tubules, Proximal/drug effects , Laboratory Proficiency Testing , Liver/drug effects , Toxicogenetics/methods , Transcriptome/drug effects , Carcinogens/classification , Cell Line, Tumor , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Genome-Wide Association Study , Humans , Kidney Tubules, Proximal/metabolism , Liver/metabolism , Observer Variation , Oligonucleotide Array Sequence Analysis , Reproducibility of Results , Risk Assessment , Time Factors , Workflow
8.
Rev Esp Med Nucl Imagen Mol ; 35(5): 287-91, 2016.
Article in English, Spanish | MEDLINE | ID: mdl-26670326

ABSTRACT

BACKGROUND: The local recurrence of pancreatic cancer is around 30% when complete resection can be achieved. Extended lymphatic resections may improve survival, but increases severe morbidity. As accurate patient selection should be mandatory, a new method is presented for pancreatic sentinel lymph node (SLN) detection with lymphoscintigraphy and gamma probe. MATERIALS AND METHODS: Seven patients with cT2N0M0 pancreatic head cancer were enrolled between 2009 and 2012 in this prospective study. One day prior to surgery, preoperative lymphoscintigraphy with echoendoscopic intratumoural administration of Tc(99m)-labelled nanocolloid was performed, with planar and SPECT-CT images obtained 2h later. Gamma probe detection of SLN was also carried out during surgery. RESULTS: Radiotracer administration was feasible in all patients. Scintigraphy images showed inter-aortocaval lymph nodes in 2 patients, hepatoduodenal ligament lymph nodes in 1, intravascular injection in 3, intestinal transit in 5, and main pancreatic duct visualisation in 1. Surgical resection could only be achieved in 4 patients owing to locally advanced disease. Intraoperative SLN detection was accomplished in 2 patients, both with negative results. Only in one patient could SLN be confirmed as truly negative by final histopathological analysis. CONCLUSIONS: This new method of pancreatic SLN detection is technically feasible, but challenging. Our preliminary results with 7 patients are not sufficient for clinical validation.


Subject(s)
Lymphoscintigraphy , Pancreatic Neoplasms/diagnostic imaging , Sentinel Lymph Node/diagnostic imaging , Humans , Prospective Studies
9.
Equine Vet J ; 48(2): 240-5, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25557934

ABSTRACT

REASONS FOR PERFORMING STUDY: Captive breeding has played a crucial role in the conservation of threatened equid species. Grazing ruminants and rhinoceros in captivity have less abrasion-dominated tooth wear than their free-ranging conspecifics, with potential negative consequences for their health. However, a similar study on wild equids in captivity is missing. OBJECTIVES: The aim was to establish if different tooth wear patterns are exhibited by free-ranging and captive equids. STUDY DESIGN: Cross-sectional study of museum specimens comparing free-ranging and captive equids. METHODS: Dental casts of maxillary cheek teeth of 228 museum specimens (122 from free-ranging and 106 from captive individuals) of 7 wild equid species were analysed using the extended mesowear method. Although teeth showing specific abnormalities were not scored, the presence of focal overgrowths (hooks) of the rostral premolars (106, 206) was recorded. RESULTS: Captive Equus ferus przewalskii, E. grevyi, E. hemionus, E. quagga boehmi and E. zebra hartmannae have less abrasion-dominated tooth wear on their premolars than their free-ranging conspecifics (P<0.001). Fewer differences were exhibited between populations in the molars. No differences were exhibited in the distal cusp of the molars (110, 210) between populations, except in a small sample of E. kiang. Captive equids exhibited more homogeneous wear along the tooth row whereas free-ranging equids exhibited a tooth wear gradient, with more abrasion on premolars than molars. There were more rostral hooks on the premolars (106, 206) in the captive than the free-ranging population (P = 0.02). CONCLUSIONS: Captive equids did experience less abrasion-dominated tooth wear than their free-ranging conspecifics, but the differences in tooth wear were less pronounced than those between captive and free-ranging wild ruminant and rhinoceros species. This indicates that feeding regimes for captive equids deviate less from natural diets than those for captive ruminants and rhinoceros but that factors leading to hook formation, in particular feeding height, should receive special attention. The Summary is available in Chinese - see Supporting information.


Subject(s)
Equidae/physiology , Tooth Wear , Animals , Animals, Wild , Species Specificity
10.
Nanotoxicology ; 9 Suppl 1: 118-32, 2015 May.
Article in English | MEDLINE | ID: mdl-25923349

ABSTRACT

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.


Subject(s)
Nanomedicine/methods , Nanoparticles/toxicity , Toxicity Tests/methods , Humans , In Vitro Techniques/standards , Toxicity Tests/standards
11.
Plant Biol (Stuttg) ; 17(5): 973-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25683278

ABSTRACT

Leaf senescence is characterised by a massive degradation of proteins in order to recycle nitrogen to other parts of the plant, such as younger leaves or developing grain/seed. Protein degradation during leaf senescence is a highly regulated process and it is suggested that proteins to be degraded are marked by an oxidative modification (carbonylation) that makes them more susceptible to proteolysis. However, there is as yet no evidence of an increase in protein carbonylation level during natural leaf senescence. The aim of our study was thus to monitor protein carbonylation level during the process of natural senescence in the flag leaf of field-grown winter wheat plants. For this purpose, we adapted a fluorescence-based method using fluorescein-5-thiosemicarbazide (FTC) as a probe for detecting protein carbonyl derivatives. As used for the first time on plant material, this method allowed the detection of both quantitative and qualitative modifications in protein carbonyl levels during the last stages of wheat flag leaf development. The method described herein represents a convenient, sensitive and reproducible alternative to the commonly used 2,4-dinitrophenylhydrazine (DNPH)-based method. In addition, our analysis revealed changes in protein carbonylation level during leaf development that were associated with qualitative changes in protein abundance and carbonylation profiles. In the senescing flag leaf, protein carbonylation increased concomitantly with a stimulation of endoproteolytic activity and a decrease in protein content, which supports the suggested relationship between protein oxidation and proteolysis during natural leaf senescence.


Subject(s)
Fluoresceins/chemistry , Protein Carbonylation , Triticum/physiology , Cellular Senescence , Edible Grain/physiology , Nitrogen/metabolism , Phenylhydrazines/chemistry , Plant Leaves/physiology , Sensitivity and Specificity , Staining and Labeling
12.
Oncogene ; 34(23): 3011-22, 2015 Jun 04.
Article in English | MEDLINE | ID: mdl-25220416

ABSTRACT

c-Myc transcription factor is a key protein involved in cellular growth, proliferation and metabolism. c-Myc is one of the most frequently activated oncogenes, highlighting the need to identify intracellular molecules that interact directly with c-Myc to suppress its function. Here we show that Hhex is able to interact with the basic region/helix-loop-helix/leucine zipper of c-Myc. Knockdown of Hhex increases proliferation rate in hepatocellular carcinoma cells, whereas Hhex expression cell-autonomously reduces cell proliferation rate in multiple cell lines by increasing G1 phase length through a c-Myc-dependent mechanism. Global transcriptomic analysis shows that Hhex counter-regulates multiple c-Myc targets involved in cell proliferation and metabolism. Concomitantly, Hhex expression leads to reduced cell size, lower levels of cellular RNA, downregulation of metabolism-related genes, decreased sensitivity to methotrexate and severe reduction in the ability to form tumours in nude mouse xenografts, all indicative of decreased c-Myc activity. Our data suggest that Hhex is a novel regulator of c-Myc function that limits c-Myc activity in transformed cells.


Subject(s)
Carcinoma, Hepatocellular/pathology , Homeodomain Proteins/metabolism , Liver Neoplasms/pathology , Proto-Oncogene Proteins c-myc/metabolism , Transcription Factors/metabolism , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation , Cell Size , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Mice , Mice, Nude , Molecular Sequence Data , NIH 3T3 Cells , Neoplasm Transplantation , Proto-Oncogene Proteins c-myc/genetics
13.
An Pediatr (Barc) ; 79(6): 390.e1-8, 2013 Dec.
Article in Spanish | MEDLINE | ID: mdl-23895944

ABSTRACT

Liver transplantation has been remarkably effective in the treatment of patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the main limitation, resulting in longer waiting times and an increase in the mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation. Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients, a bridge to restore liver function or liver transplant. The procedure consists in transplanting individual cells in a recipient organ in enough quantity to survive and restore the function. The capacity of hepatic regeneration constitutes the biological basis of hepatocyte transplantation. Liver cell transplantation is carried out by means of the isolation of hepatocytes from donor liver rejected for orthotopic transplantation, to prepare a cell suspension for infusion, cryopreservation and, finally, hepatocytes are implanted into the recipient. This may be an optional therapeutic procedure in some patients with inborn errors of metabolism, fulminant hepatic failure, and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. The first hepatocyte transplantation in Spain was performed in the Cell Therapy Unit of the Hospital La Fe of Valencia, creating a new research line in the transplant program.


Subject(s)
Hepatocytes/transplantation , Metabolism, Inborn Errors/surgery , Child , Female , Humans , Infant , Male
14.
Eur Surg Res ; 50(3-4): 273-81, 2013.
Article in English | MEDLINE | ID: mdl-23796722

ABSTRACT

BACKGROUND: Hepatocyte transplantation (HT) has the potential to become a promising treatment to temporarily support liver function in patients with liver failure. METHODS: Two patients, who had already received a liver transplant (LT) in the past, with an end-stage liver disease due to recurrent hepatitis C virus cirrhosis, suffering acute-on-chronic liver failure while on the waiting list for an LT, received HT as a bridge to whole-organ retransplantation. After HT and during intensive care unit admission, blood tests and ammonia levels were determined every 12 and 24 h, respectively, before and after each hepatocyte infusion. RESULTS: The present study describes monitoring of analytical and clinical parameters and improvement of liver function following HT. In both patients, we managed to lower the blood ammonia levels and clinically improve the degree of hepatic encephalopathy, thus serving as a bridge to liver retransplantation in 1 patient. CONCLUSIONS: We believe that this therapy may be an alternative treatment in patients with chronic liver disease who suffer episodes of acute decompensation as a bridge to conventional LT.


Subject(s)
End Stage Liver Disease/surgery , End Stage Liver Disease/therapy , Hepatocytes/transplantation , Liver Transplantation , Adult , Ammonia/blood , End Stage Liver Disease/physiopathology , Hepatitis C, Chronic/physiopathology , Hepatitis C, Chronic/surgery , Hepatitis C, Chronic/therapy , Hepatocytes/cytology , Hepatocytes/physiology , Humans , Liver Function Tests , Male , Middle Aged , Reoperation , Time Factors , Waiting Lists
15.
Toxicol In Vitro ; 27(2): 954-63, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23357416

ABSTRACT

No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay for detection of oxidative species. In the present research, nanomaterial interaction with DCFH-DA was studied in relation to its nature and/or assay conditions (cell-based and time exposure) by incubating Rhodamine (Rhd)-labeled 25nm and 50nm silica (SiO2), naked and oleic acid coated magnetite, (Fe3O4) and maghemite (Fe2O3) iron oxide, titanium dioxide (TiO2) and poly(ethylene oxide)-poly(lactide/glycolide) acid (PLGA-PEO) nanoparticles (NPs) with metabolically active rat hepatocytes for 4 and 24-h periods. Data indicated that nanoparticle uptake correlated with quenching of dye fluorescence emission. In spite of their masking effect, the oxidative potential of NPs could be detected at a limited threshold concentration when exposed for periods of time longer than those frequently used for this test. However, changes in the experimental conditions did not systematically result in free radical formation for all nanomaterials tested. Overall data indicate that despite the quenching effect of nanoparticles on DCFH-DA assay, it can be considered as a useful tool for quantitative measurement of NPs-induced oxidative stress by minor modifications of standardized protocols.


Subject(s)
Biological Assay/methods , Fluoresceins , Fluorescent Dyes , Nanoparticles/toxicity , Oxidative Stress/drug effects , Animals , Cell Survival/drug effects , Cells, Cultured , Ferric Compounds/toxicity , Ferrosoferric Oxide/toxicity , Hepatocytes , Lactic Acid/toxicity , Male , Polyethylene Glycols/toxicity , Polyglycolic Acid/toxicity , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Silicon Dioxide/toxicity , Titanium/toxicity
16.
Mutat Res ; 750(1-2): 34-9, 2013 Jan 20.
Article in English | MEDLINE | ID: mdl-23022340

ABSTRACT

The role of different DNA-repair genes (OGG1, XRCC1, XRCC2 and XRCC3) on both the spontaneous and the induced frequency of micronuclei (MN) has been studied in the lymphocytes of a group of 114 patients with differentiated thyroid cancer (DTC). Induction of MN was achieved by treatment of the lymphocytes with 0.5Gy of gamma-radiation. The selected genes are involved in base-excision repair (BER) (OGG1, Ser326Cys; XRCC1, Arg280His and Arg399Gln), and in homologous recombination repair (HRR) (XRCC2, Arg188His and XRCC3, IVS5-14G). Genotyping was carried out by use of the iPLEX (Sequenom) technique. Results indicate that only the OGG1-Ser326Cys polymorphism was able to modulate the MN frequency. This effect was only observed in the spontaneous MN frequency (P=0.016), but not in the MN frequency induced after irradiation. In addition, a strong correlation was observed between spontaneous and induced MN frequency, which would suggest an underlying genetic background.


Subject(s)
DNA Repair Enzymes/genetics , Micronuclei, Chromosome-Defective , Polymorphism, Single Nucleotide , Thyroid Neoplasms/genetics , Adult , DNA Damage , Female , Humans , Male , Middle Aged
17.
Actas urol. esp ; 36(4): 239-245, abr. 2012. tab
Article in Spanish | IBECS | ID: ibc-101145

ABSTRACT

Objetivo: Revisar los factores de riesgo (FR) dietéticos implicados, con mayor o menor evidencia científica, en la etiopatogenia del carcinoma de próstata (CP), especialmente los característicos de la tradicional dieta mediterránea (DM). Material y métodos: Revisión bibliográfica de los FR dietéticos asociados al CP obtenida de MedLine, CancerLit, Science Citation Index y Embase. Los perfiles de búsqueda han sido Dietetic Factors/ Nutritional Factors/ Mediterranean Diet/ Primary Prevention y Prostate Cancer. Resultados: Los FR dietéticos se asocian al 35% de las muertes por cáncer y al 10-12% del CP. Los principales FR dietéticos, implicados en el CP y característicos de la DM, son los siguientes: ingesta diaria y elevada de alimentos vegetales (cereales, legumbres, frutas frescas-secas, tubérculos, verduras, etc.); consumo de aceite de oliva como lípido habitual; baja ingesta de grasa saturada animal, carne roja y procesada, leche y derivados; consumo regular de pescado pequeño; y escaso consumo alcohólico (vino en las comidas). La DM proporciona numerosos compuestos fitoactivos (licopeno, lupeol, quercetina, genisteína, carnosol, resveratrol, catequinas, vitaminas, etc.) con efectos protectores del CP. Conclusiones: Los FR dietéticos influencian la carcinogénesis prostática. Para conocer con más exactitud los FR dietéticos implicados en el CP son necesarios mejores diseños epidemiológicos. La mayor adherencia a la DM, en contraste con las dietas occidentales, se asocia a menor riesgo de CP. El denominador común del efecto preventivo de la DM se basa en la gran cantidad y calidad de fitoquímicos con propiedades antioxidantes y antiinflamatorias (AU)


Objective: To review diet risk factors (RF) implied, more or less evidence-based, in the etiopathology of prostate carcinoma (PC), especially those that characterize the traditional mediterranean diet (MD). Material and methods: Literature review of PC related diet RF in MedLine, CancerLit, Science Citation Index y Embase. Search profiles were "Dietetic Factors/Nutritional Factors/Mediterranean Diet/Primary Prevention", and "Prostate Cancer". Results: Diet RF are associated with 35% of cancer mortality and 10-12% of PC mortality. The main diet RF, implied in the development of PC but with a protective effect, which are considered characteristic of MD are: high daily ingestion of vegetarian products (cereals, legums, dried and fresh fruits, tubercles, vegetables..); olive oil as main lipid source; low intake of animal saturated fat, processed red meat, milk and dairy products; regular consumption of small fish; and low alcohol intake (wine with meals). The MD contains many phytoactive compounds (lycopene, lupeol, quercetin, genistein, carnosol, resveratrol, catechins, vitamins...) with PC protective effects. Conclusions: Diet RF have a role on prostatic carcinogenesis. Further epidemiologic studies with better designs are needed to clarify PC related diet RF. PC risk is reduced in persons on MD compared with those on western diet. The preventive effect of MD is due to the great number and quality of phytochemicals with antioxidant and antinflammatory properties that contains (AU)


Subject(s)
Humans , Male , Diet, Mediterranean , Prostatic Neoplasms/diet therapy , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/prevention & control , Evidence-Based Medicine/methods , Risk Factors , Prostatic Neoplasms/etiology , Prostatic Neoplasms/physiopathology , Antioxidants/therapeutic use
18.
Actas Urol Esp ; 36(4): 239-45, 2012 Apr.
Article in Spanish | MEDLINE | ID: mdl-21959061

ABSTRACT

OBJECTIVE: To review diet risk factors (RF) implied, more or less evidence-based, in the etiopathology of prostate carcinoma (PC), especially those that characterize the traditional Mediterranean diet (MD). MATERIAL AND METHODS: Literature review of PC related diet RF in MedLine, CancerLit, Science Citation Index y Embase. Search profiles were "Dietetic Factors/Nutritional Factors/Mediterranean Diet/Primary Prevention", and "Prostate Cancer". RESULTS: Diet RF are associated with 35% of cancer mortality and 10-12% of PC mortality. The main diet RF, implied in the development of PC but with a protective effect, which are considered characteristic of MD are: high daily ingestion of vegetarian products (cereals, legumes, dried and fresh fruits, tubers, vegetables..); olive oil as main lipid source; low intake of animal saturated fat, processed red meat, milk and dairy products; regular consumption of small fish; and low alcohol intake (wine with meals). The MD contains many phytoactive compounds (lycopene, lupeol, quercetin, genistein, carnosol, resveratrol, catechins, vitamins..) with PC protective effects. CONCLUSIONS: Diet RF have a role on prostatic carcinogenesis. Further epidemiologic studies with better designs are needed to clarify PC related diet RF. PC risk is reduced in persons on MD compared with those on Western diet. The preventive effect of MD is due to the great number and quality of phytochemicals with antioxidant and antinflammatory properties that contains.


Subject(s)
Adenocarcinoma/prevention & control , Anticarcinogenic Agents/administration & dosage , Diet, Mediterranean , Prostatic Neoplasms/prevention & control , Adenocarcinoma/epidemiology , Adenocarcinoma/etiology , Animals , Antioxidants/administration & dosage , Carotenoids/administration & dosage , Dietary Fats/adverse effects , Dietary Fats, Unsaturated/administration & dosage , Fishes , Flavonoids/administration & dosage , Humans , Life Style , Male , Meat/adverse effects , Phytoestrogens/administration & dosage , Polyphenols/administration & dosage , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/etiology , Vegetables , Wine
20.
Mar Pollut Bull ; 63(1-4): 18-26, 2011.
Article in English | MEDLINE | ID: mdl-21665016

ABSTRACT

The development and broad use of passive acoustic monitoring techniques have the potential to help assessing the large-scale influence of artificial noise on marine organisms and ecosystems. Deep-sea observatories have the potential to play a key role in understanding these recent acoustic changes. LIDO (Listening to the Deep Ocean Environment) is an international project that is allowing the real-time long-term monitoring of marine ambient noise as well as marine mammal sounds at cabled and standalone observatories. Here, we present the overall development of the project and the use of passive acoustic monitoring (PAM) techniques to provide the scientific community with real-time data at large spatial and temporal scales. Special attention is given to the extraction and identification of high frequency cetacean echolocation signals given the relevance of detecting target species, e.g. beaked whales, in mitigation processes, e.g. during military exercises.


Subject(s)
Environmental Monitoring/methods , Noise/adverse effects , Vocalization, Animal , Whales/physiology , Acoustics , Animals , Auditory Perception , Echolocation , Environmental Monitoring/instrumentation , Noise/prevention & control , Oceans and Seas
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