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1.
J Am Chem Soc ; 145(14): 8052-8063, 2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-36994816

RESUMEN

Single atom catalysts (SACs) possess unique catalytic properties due to low-coordination and unsaturated active sites. However, the demonstrated performance of SACs is limited by low SAC loading, poor metal-support interactions, and nonstable performance. Herein, we report a macromolecule-assisted SAC synthesis approach that enabled us to demonstrate high-density Co single atoms (10.6 wt % Co SAC) in a pyridinic N-rich graphenic network. The highly porous carbon network (surface area of ∼186 m2 g-1) with increased conjugation and vicinal Co site decoration in Co SACs significantly enhanced the electrocatalytic oxygen evolution reaction (OER) in 1 M KOH (η10 at 351 mV; mass activity of 2209 mA mgCo-1 at 1.65 V) with more than 300 h stability. Operando X-ray absorption near-edge structure demonstrates the formation of electron-deficient Co-O coordination intermediates, accelerating OER kinetics. Density functional theory (DFT) calculations reveal the facile electron transfer from cobalt to oxygen species-accelerated OER.

2.
Nanotechnology ; 31(10): 105702, 2020 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-31751978

RESUMEN

Sub-monolayer (SML) deposition of InSb within InAs matrix by migration enhanced epitaxy tends to form type II SML nanostructures offering efficient light emission within the mid-infrared (MIR) range between 3 and 5 µm. In this work, we report on the Sb distribution in InSb/InAs SML nanostructures with InAs cap layers grown at temperatures lower than that associated with the under-grown InSb active layer. Analysis by transmission electron microscopy (TEM) in 002 dark field conditions shows that the reduction in the growth temperature of the InAs cap layer increases the amount of Sb deposited in the layers, in good agreement with the x-ray diffraction results. TEM micrographs also show that the layers are formed by random InSbAs agglomerates, where the lower cap temperature leads to a more continuous InSb layer. Quantitative atomic column resolved high angle annular dark field-scanning (S)TEM analyses also reveal atomic columns with larger composition of Sb for the structure with the lowest InAs cap layer temperature. The dependence of the Sb distribution on InAs cap growth temperature allows tuning the corresponding emission wavelength in the MIR range, as shown by the photoluminescence emission spectra.

3.
Rep Pract Oncol Radiother ; 25(3): 447-455, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32477011

RESUMEN

BACKGROUND: The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined. AIM: To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014. RESULTS: 47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. "not reached" (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS. CONCLUSIONS: Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.

4.
Nano Lett ; 18(5): 3066-3075, 2018 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-29694788

RESUMEN

Nanowires are a versatile platform to investigate and harness phonon and thermal transport phenomena in nanoscale systems. With this perspective, we demonstrate herein the use of crystal phase and mass disorder as effective degrees of freedom to manipulate the behavior of phonons and control the flow of local heat in silicon nanowires. The investigated nanowires consist of isotopically pure and isotopically mixed nanowires bearing either a pure diamond cubic or a cubic-rhombohedral polytypic crystal phase. The nanowires with tailor-made isotopic compositions were grown using isotopically enriched silane precursors 28SiH4, 29SiH4, and 30SiH4 with purities better than 99.9%. The analysis of polytypic nanowires revealed ordered and modulated inclusions of lamellar rhombohedral silicon phases toward the center in otherwise diamond-cubic lattice with negligible interphase biaxial strain. Raman nanothermometry was employed to investigate the rate at which the local temperature of single suspended nanowires evolves in response to locally generated heat. Our analysis shows that the lattice thermal conductivity in nanowires can be tuned over a broad range by combining the effects of isotope disorder and the nature and degree of polytypism on phonon scattering. We found that the thermal conductivity can be reduced by up to ∼40% relative to that of isotopically pure nanowires, with the lowest value being recorded for the rhombohedral phase in isotopically mixed 28Si x30Si1- x nanowires with composition close to the highest mass disorder ( x ∼ 0.5). These results shed new light on the fundamentals of nanoscale thermal transport and lay the groundwork to design innovative phononic devices.

5.
Cir Pediatr ; 31(1): 21-24, 2018 Feb 01.
Artículo en Español | MEDLINE | ID: mdl-29419954

RESUMEN

INTRODUCTION AND OBJECTIVES: Recurrent abdominal pain is defined as > 3 episodes of abdominal pain accompanied by affectation of the daily activity, during > 3 months. Our objective is to analyze the role of diagnostic and/or therapeutic laparoscopy. MATERIAL AND METHODS: A descriptive, retrospective study from 2004 to 2016. Patients: <14 years with DAR who underwent laparoscopy. Variables: age, sex, history, surgical findings, histology and follow-up. RESULTS: 55 patients. Mean age: 10.7 years. Female 63, 6%. Probability of allergic comorbidity: 27.27% [16.138-40.962] (CI 95%). Probability of subsequent psychological comorbidity: 12.72% [5.27 -24.48] (95% CI). Histological changes 31/55 (56.36%): lymphoid nodular hyperplasia 10/31, appendicular inflammation 7/31, fecalite 3/31, carcinoid tumor 1/31, appendicular fibrosis 3/31, Meckel diverticulum 1/31, association of several of the above 8/31. Macroscopic alterations 31/55 (56.36%): appendicular pathology 10/31, adhesions 5/31, lymph nodes 2/31, ileitis 2/31, tubal cysts 1/31, Meckel 1/31 diverticulum, several of the previous ones 10/31. Remission of symptoms: 30/55 (54.54%). In some cases, with partial improvement (4/55) or persistence of symptoms (21/55), organic and/ or psychological cause was demonstrated (16/25). CONCLUSIONS: Recurrent abdominal pain seems to have a significant association with an allergic or psychological history. Exploratory laparoscopy is a useful diagnostic and therapeutic technique.


INTRODUCCION Y OBJETIVOS: El dolor abdominal recurrente (DAR) supone > 3 episodios de dolor abdominal acompañados de afectación de la actividad diaria, durante > 3 meses. Nuestro objetivo es analizar el papel de la laparoscopia diagnóstica y/o terapéutica. MATERIAL Y METODOS: Estudio descriptivo, retrospectivo desde 2004 hasta 2016. Pacientes < 14 años con DAR a los que se les practicó laparoscopia. Variables: edad, sexo, antecedentes, hallazgos quirúrgicos, histología y evolución. RESULTADOS: 55 pacientes. Media de edad: 10,7 años. Mujeres 63, 6%. Probabilidad de comorbilidad alérgica: 27,27% [16,138- 40,962] (I.C 95%). Probabilidad de comorbilidad posterior psicológica: 12,72% [5,27 -24,48] (I.C 95%). Alteraciones histológicas 31/55 (56,36%): hiperplasia nodular linfoide 10/35, inflamación apendicular 7/31, fecalito 3/31, tumor carcinoide 1/31, fibrosis apendicular 3/31, divertículo de Meckel 1/31, asociación de varios de los anteriores 8/31. Alteraciones macroscópicas 31/55 (56,36%): patología apendicular 10/31, bridas 5/31, adenopatías 2/31, ileítis 2/31, quistes tubáricos 1/31, divertículo de Meckel 1/31, varios 10/31. Remisión: 30/ 55 (54,54%). En algunos casos con mejoría parcial (sin desaparición completa del dolor) (4/55) o persistencia de síntomas (21/55) se demostró causa orgánica y/o psicológica (16/25). CONCLUSIONES: El dolor abdominal recurrente parece presentar una asociación significativa con antecedentes alérgicos o psicológicos. La laparoscopia exploradora supone una técnica diagnóstica y terapéutica.


Asunto(s)
Dolor Abdominal/terapia , Hipersensibilidad/complicaciones , Laparoscopía/métodos , Trastornos Mentales/complicaciones , Dolor Abdominal/etiología , Dolor Abdominal/psicología , Adolescente , Niño , Preescolar , Femenino , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/epidemiología , Humanos , Hipersensibilidad/epidemiología , Masculino , Trastornos Mentales/epidemiología , Recurrencia , Estudios Retrospectivos
6.
Br J Haematol ; 172(5): 786-93, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26898196

RESUMEN

The clinical significance of resistance/intolerance to hydroxycarbamide (HC) was assessed in a series of 890 patients with polycythaemia vera (PV). Resistance/intolerance to HC was recorded in 137 patients (15·4%), consisting of: need for phlebotomies (3·3%), uncontrolled myeloproliferation (1·6%), failure to reduce massive splenomegaly (0·8%), development of cytopenia at the lowest dose of HC to achieve a response (1·7%) and extra-haematological toxicity (9%). With a median follow-up of 4·6 years, 99 patients died, resulting in a median survival of 19 years. Fulfilling any of the resistance/intolerance criteria had no impact on survival but when the different criteria were individually assessed, an increased risk of death was observed in patients developing cytopenia [Hazard ratio (HR): 3·5, 95% confidence interval (CI): 1·5-8·3, P = 0·003]. Resistance/intolerance had no impact in the rate of thrombosis or bleeding. Risk of myelofibrotic transformation was significantly higher in those patients developing cytopenia (HR: 5·1, 95% CI: 1·9-13·7, P = 0·001) and massive splenomegaly (HR: 9·1, 95% CI: 2·3-35·9, P = 0·002). Cytopenia at the lowest dose required to achieve a response was also an independent risk factor for transformation to acute leukaemia (HR: 20·3, 95% CI: 5·4-76·5, P < 0·001). In conclusion, the unified definition of resistance/intolerance to HC delineates a heterogeneous group of PV patients, with those developing cytopenia being associated with an adverse outcome.


Asunto(s)
Hidroxiurea/uso terapéutico , Inhibidores de la Síntesis del Ácido Nucleico/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Medicamentos , Tolerancia a Medicamentos , Femenino , Humanos , Hidroxiurea/efectos adversos , Estimación de Kaplan-Meier , Recuento de Leucocitos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Inhibidores de la Síntesis del Ácido Nucleico/efectos adversos , Policitemia Vera/sangre , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
Nano Lett ; 15(6): 3885-93, 2015 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-25993500

RESUMEN

The introduction of stable isotopes in the fabrication of semiconductor nanowires provides an additional degree of freedom to manipulate their basic properties, design an entirely new class of devices, and highlight subtle but important nanoscale and quantum phenomena. With this perspective, we report on phonon engineering in metal-catalyzed silicon nanowires with tailor-made isotopic compositions grown using isotopically enriched silane precursors (28)SiH4, (29)SiH4, and (30)SiH4 with purity better than 99.9%. More specifically, isotopically mixed nanowires (28)Si(x)(30)Si(1-x) with a composition close to the highest mass disorder (x ∼ 0.5) were investigated. The effect of mass disorder on the phonon behavior was elucidated and compared to that in isotopically pure (29)Si nanowires having a similar reduced mass. We found that the disorder-induced enhancement in phonon scattering in isotopically mixed nanowires is unexpectedly much more significant than in bulk crystals of close isotopic compositions. This effect is explained by a nonuniform distribution of (28)Si and (30)Si isotopes in the grown isotopically mixed nanowires with local compositions ranging from x = ∼0.25 to 0.70. Moreover, we also observed that upon heating, phonons in (28)Si(x)(30)Si(1-x) nanowires behave remarkably differently from those in (29)Si nanowires suggesting a reduced thermal conductivity induced by mass disorder. Using Raman nanothermometry, we found that the thermal conductivity of isotopically mixed (28)Si(x)(30)Si(1-x) nanowires is ∼30% lower than that of isotopically pure (29)Si nanowires in agreement with theoretical predictions.


Asunto(s)
Nanocables/química , Fonones , Silicio/química , Silanos/química
8.
Nano Lett ; 14(3): 1665-73, 2014 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-24502703

RESUMEN

We report the observation of transverse-magnetic-polarized infrared absorption assigned to the s-p(z) intraband transition in Ge-doped GaN/AlN nanodisks (NDs) in self-assembled GaN nanowires (NWs). The s-p(z) absorption line experiences a blue shift with increasing ND Ge concentration and a red shift with increasing ND thickness. The experimental results in terms of interband and intraband spectroscopy are compared to theoretical calculations of the band diagram and electronic structure of GaN/AlN heterostructured NWs, accounting for their three-dimensional strain distribution and the presence of surface states. From the theoretical analysis, we conclude that the formation of an AlN shell during the heterostructure growth applies a uniaxial compressive strain which blue shifts the interband optical transitions but has little influence on the intraband transitions. The presence of surface states with density levels expected for m-GaN plane charge-deplete the base of the NWs but is insufficient to screen the polarization-induced internal electric field in the heterostructures. Simulations show that the free-carrier screening of the polarization-induced internal electric field in the NDs is critical to predicting the photoluminescence behavior. The intraband transitions, on the other hand, are blue-shifted due to many-body effects, namely, the exchange interaction and depolarization shift, which exceed the red shift induced by carrier screening.

9.
Tissue Antigens ; 84(6): 545-53, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25413104

RESUMEN

Celiac disease (CD) is a complex autoimmune disorder caused by ingestion of gluten in genetically susceptible individuals. Different genetic risk factors have been identified, but virtually all patients are human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive. We describe a new, fast, accurate and simple real-time polymerase chain reaction (PCR)-based assay for the genotyping and homozygosity analysis of the CD-related HLA alleles. The assay overcomes the major limitations of protocols currently in use, allowing HLA-DQ2/DQ8 genotyping by using only three real-time PCR reactions. For the appraisal of DQ2 homozygosity, only one more reaction is needed. These reactions are easily automated and suitable for large screening studies in diagnostic procedures, as it is demonstrated by their successful application in our HLA diagnostic laboratory. Finally, we assessed the clinical relevance of this real-time PCR-based assay by studying a cohort of fully characterized patients. As expected, all CD patients had at least one of the CD-associated alleles, and the highest CD risk was indicated by the presence of the HLA-DQ2.5 heterodimer (HLA-DQA1*05-DQB1*02) with HLA-DQB1*02 in homozygosity.


Asunto(s)
Alelos , Enfermedad Celíaca/genética , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Enfermedad Celíaca/epidemiología , Femenino , Homocigoto , Humanos , Masculino , Factores de Riesgo , España/epidemiología
10.
Ann Hematol ; 93(12): 2037-43, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24981691

RESUMEN

Therapeutic options for patients with polycythemia vera (PV) and essential thrombocythemia (ET) resistant or intolerant to hydroxyurea are limited. Busulfan is effective as first-line therapy, but there is scarce information on this drug as second-line treatment. The efficacy of busulfan in patients with advanced PV or ET refractory or intolerant to hydroxyurea was assessed in 36 patients (PV n = 15, ET n = 21) treated for a median of 256 days. Complete hematological response (CHR) was achieved in 83 % of patients, after a median time of 203 days (range 92-313). The probability of sustained CHR at 1 and 2 years was 87 and 62 %, respectively. Time to CHR was shorter in patients treated with ≥14 mg of busulfan per week than with lower doses (141 versus 336 days, p = 0.01). Partial molecular response was achieved in three out of nine (33 %) patients. Busulfan was stopped in 27 patients (75 %) due to CHR achievement in 18 cases (67 %), hematological toxicity in 8 cases (30 %), and disease transformation in 1 case. With a median follow-up of 721 days, six patients have died, with the probability of survival at 2 years being 85 %. The probability of thrombosis at 2 years was 11 %. Transformation into acute leukemia or myelodysplastic syndrome was observed in three cases, all of them in a JAK2V617F-negative clone carrying additional mutations. Busulfan, at a dose of 2 mg/day, is an effective option for elderly patients with PV or ET who fail to hydroxyurea, but a significant rate of transformation was observed.


Asunto(s)
Alquilantes/uso terapéutico , Busulfano/uso terapéutico , Policitemia Vera/tratamiento farmacológico , Trombocitemia Esencial/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Recuento de Células Sanguíneas , Comorbilidad , Progresión de la Enfermedad , Resistencia a Medicamentos , Sustitución de Medicamentos , Femenino , Hematócrito , Hemorragia/etiología , Humanos , Hidroxiurea/efectos adversos , Hidroxiurea/uso terapéutico , Janus Quinasa 2/genética , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Masculino , Persona de Mediana Edad , Policitemia Vera/complicaciones , Policitemia Vera/genética , Inducción de Remisión , Factores de Riesgo , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/genética , Trombosis/etiología , Resultado del Tratamiento
11.
J Biol Regul Homeost Agents ; 27(2): 337-50, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23830385

RESUMEN

Analysis of gene-expression profiles by microarrays is useful for characterization of candidate genes, key regulatory networks, and to define phenotypes or molecular signatures which improve the diagnosis and/or classification of the allergic processes. We have used this approach in the study of olive pollen response in order to find differential molecular markers among responders and non-responders to this allergenic source. Five clinical groups, non-allergic, asymptomatic, allergic but not to olive pollen, untreated-olive-pollen allergic patients and olive-pollen allergic patients (under specific-immunotherapy), were assessed during and outside pollen seasons. Whole-genome gene expression analysis was performed in RNAs extracted from PBMCs. After assessment of data quality and principal components analysis (PCA), differential gene-expression, by multiple testing and, functional analyses by KEGG, for pathways and Gene-Ontology for biological processes were performed. Relevance was defined by fold change and corrected P values (less than 0.05). The most differential genes were validated by qRT-PCR in a larger set of individuals. Interestingly, gene-expression profiling obtained by PCA clearly showed five clusters of samples that correlated with the five clinical groups. Furthermore, differential gene expression and functional analyses revealed differential genes and pathways in the five clinical groups. The 93 most significant genes found were validated, and one set of 35 genes was able to discriminate profiles of olive pollen response. Our results, in addition to providing new information on allergic response, define a possible molecular signature for olive pollen allergy which could be useful for the diagnosis and treatment of this and other sensitizations.


Asunto(s)
Perfilación de la Expresión Génica , Olea/inmunología , Rinitis Alérgica Estacional/genética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Componente Principal
12.
Cir Pediatr ; 36(1): 44-47, 2023 Jan 01.
Artículo en Inglés, Español | MEDLINE | ID: mdl-36629349

RESUMEN

BACKGROUND: Disseminated intravascular coagulation (DIC) is a rare oncological emergency. We report a pediatric neuroblastoma complicated with DIC which required thromboelastometry-guided surgery. OBSERVATION: A 6-year-old female diagnosed with intermediate risk adrenal neuroblastoma developed tumor-related DIC after chemotherapy first cycle. She remained stable without clinical bleeding and emergent tumor resection guided by intraoperative-thromboelastometry was decided. DIC resolved early after surgery and complete remission was achieved. CONCLUSION: Treatment of the underlying condition is critical to manage DIC. Thromboelastometry can guide goal-directed therapy, including surgery in pediatric patients. However, larger studies are needed to examine its applicability in different clinical settings, such as cancer related DIC.


INTRODUCCION: La coagulación intravascular diseminada (CID) es una urgencia oncológica poco común. Describimos el caso de un neuroblastoma pediátrico complicado con CID que precisó de cirugía guiada por tromboelastometría. CASO CLINICO: Paciente de seis años diagnosticada de neuroblastoma suprarrenal de riesgo intermedio que desarrolló CID asociada al tumor tras el primer ciclo de quimioterapia. Permaneció estable sin hemorragia clínica, decidiéndose una resección tumoral de urgencia guiada por tromboelastometría intraoperatoria. La CID se resolvió poco después de la cirugía, consiguiéndose una remisión total. CONCLUSION: El tratamiento de la patología subyacente es clave a la hora de manejar la CID. La tromboelastometría puede guiar la terapia orientada a objetivos, también en cirugías realizadas en pacientes pediátricos. No obstante, hacen falta mayores estudios que analicen su aplicabilidad en distintos contextos clínicos, como la CID relacionada con cáncer.


Asunto(s)
Coagulación Intravascular Diseminada , Neuroblastoma , Femenino , Humanos , Niño , Tromboelastografía/efectos adversos , Coagulación Intravascular Diseminada/complicaciones , Neuroblastoma/complicaciones , Neuroblastoma/cirugía
13.
Food Res Int ; 173(Pt 1): 113244, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803557

RESUMEN

Plant-based beverages (PBB) market is largely growing. In this study, 136 beverages made of soy, oat, almond, rice, tigernut, and others (mixtures of various plant materials), from the Spanish market were evaluated through labelling information. Energy value and fat content were intermediate between skimmed and whole cow milk; while fatty acids profile was quite different. Carbohydrate content was usually higher than cow milk, and highly dependent on the addition of sugars. All products provided some dietary fibre. With the exception of soy-based drinks, samples presented lower protein and calcium content than milk (1/3 samples studied were Ca-fortified), and 23% were vitamin D enriched. The claim "No added sugars" was in more than 50% samples. A right labelling and nutritional education of consumers is essential to make adequate choices, since the appearing of many claims is not always indicative of a better-quality product. Plant-based beverages cannot be considered as an alternative to milk, but as a different product, with their own nutritional and functional entity. Their inclusion in a diversified balanced diet can provide interesting functional components, such as soluble fibre or unsaturated fatty acids (mainly soybean and almond drink), which can help improve the health status of the population.


Asunto(s)
Etiquetado de Alimentos , Leche , Femenino , Animales , Bovinos , Bebidas , Vitaminas , Azúcares
14.
Gene Ther ; 19(11): 1107-13, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22089494

RESUMEN

We previously reported regulated expression of erythropoietin (EPO) over 4 weeks in the peripheral nerve in vivo, using a herpes simplex virus (HSV)-based vector containing a Tet-on regulatable gene expression cassette. To create a vector that would be appropriate for the treatment of chronic neuropathy, we constructed a HSV vector with expression of EPO under the control of the Tet-on system in which the HSV latency-associated promoter 2 element was used to drive the expression of the Tet-on transactivator. EPO expression from the vector was tightly controlled by administration of doxycycline (DOX) in vitro. One month after inoculation of the vector to transduce dorsal root ganglion (DRG) in vivo, administration of DOX-containing chow-induced expression of EPO. Mice with streptozotocin-induced diabetes, inoculated with the vector, were protected against the development of neuropathy by continuous administration of DOX-containing chow over the course of 3 months. Identical results were achieved when DOX was administered every other week over 3 months of diabetes, but administration of DOX, 1 week out of 3, provided only partial protection against the development of neuropathy. Taken together, these results suggest such a vector is well suited for clinical trial for the treatment of chronic or subacutely developing neuropathy.


Asunto(s)
Proteínas de Unión al ADN/genética , Eritropoyetina/genética , Regulación de la Expresión Génica , Vectores Genéticos/genética , Proteínas de la Membrana/genética , Regiones Promotoras Genéticas , Simplexvirus/genética , Animales , Línea Celular , Neuropatías Diabéticas/genética , Neuropatías Diabéticas/terapia , Progresión de la Enfermedad , Doxiciclina/farmacología , Eritropoyetina/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Orden Génico , Terapia Genética , Humanos , Masculino , Ratones
15.
Gene Ther ; 19(1): 101-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21614028

RESUMEN

Opiate/narcotic analgesics are the most effective treatments for chronic severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. Recent evidence suggests chronic morphine may activate glial cells to release proinflammatory cytokines. In this study, we used herpes simplex virus (HSV) vector-based gene transfer to dorsal root ganglion to produce a local release of p55 tumor necrosis factor (TNF) soluble receptor in the spinal cord in rats with morphine tolerance. Subcutaneous inoculation of HSV vectors expressing p55 TNF soluble receptor into the plantar surface of the hindpaws enhanced the antinociceptive effect of acute morphine in rats. Subcutaneous inoculation of those vectors into hindpaws also delayed the development of chronic morphine tolerance in rats. TNF soluble receptor expressed by HSV vector reduced gene transcription of spinal TNFα and interleukin-1ß (IL-1ß) induced by repeated morphine. Furthermore, we found that TNF soluble receptor mediated by HSV reversed the upregulation of protein level of TNFα and IL-1ß and phosphorylation of p38 mitogen-activated protein kinase induced by repeated morphine. These results support the concept that proinflammatory cytokines may have an important role in the pathogenesis induced by morphine. This study provides a novel approach to treating morphine tolerance.


Asunto(s)
Tolerancia a Medicamentos , Morfina/farmacología , Receptores del Factor de Necrosis Tumoral/inmunología , Transgenes , Analgésicos/administración & dosificación , Analgésicos/farmacología , Animales , Conducta Animal , Ganglios Espinales/inmunología , Ganglios Espinales/metabolismo , Regulación de la Expresión Génica , Técnicas de Transferencia de Gen , Terapia Genética , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Vectores Genéticos/metabolismo , Inyecciones Subcutáneas , Interleucina-1beta/inmunología , Masculino , Morfina/administración & dosificación , Fosforilación , Ratas , Ratas Sprague-Dawley , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Simplexvirus/genética , Simplexvirus/inmunología , Simplexvirus/metabolismo , Médula Espinal/inmunología , Médula Espinal/metabolismo , Factores de Tiempo , Transcripción Genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
16.
Gene Ther ; 19(9): 907-14, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22052241

RESUMEN

We evaluated the therapeutic effect of erythropoietin (EPO) delivered by direct injection of a nonreplicating herpes simplex virus (HSV)-based vector coding for EPO (vEPO) in a model of cervical hemicord contusion at C7. At 1 h after spinal cord injury (SCI), either vEPO or control vector carrying a reporter gene (vC) was injected into the cord above and below the lesion. Animals injected with vEPO showed a statistically significant improvement in the ipsilateral forelimb function, as measured by open-field evaluation of motor performance, forelimb reaching in the cylinder test and misplacement in grid walk. This correlated with preservation of gray matter in the area of the lesion. There was also mild but significant improvement of hindlimb motor function measured by Basso-Beattie-Bresnahan score and computerized gait analysis in vEPO compared with control vector-injected animals. Microtubule-associated protein tau, phosphorylated and nonphosphorylated neurofilament protein and the synaptic proteins synaptophysin and PSD-95 were all significantly increased in the spinal cord of vEPO-treated animals compared with control vector-injected animals. These data suggest that gene transfer of EPO after cervical SCI by minimizing the injury size and enhancing tissue sparing preserves large-caliber axons and promotes synaptogenesis.


Asunto(s)
Contusiones/terapia , Eritropoyetina/genética , Vectores Genéticos , Simplexvirus/genética , Traumatismos de la Médula Espinal/terapia , Transfección , Animales , Femenino , Miembro Anterior/fisiopatología , Miembro Posterior/fisiopatología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas de Neurofilamentos/metabolismo , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Médula Espinal/citología , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/fisiopatología
17.
Am J Transplant ; 12(9): 2465-76, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22703615

RESUMEN

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.


Asunto(s)
Infecciones por VIH/cirugía , Hepatitis C/cirugía , Trasplante de Hígado , Reoperación , Adulto , Femenino , Infecciones por VIH/complicaciones , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , ARN Viral/aislamiento & purificación , Análisis de Supervivencia
18.
J Exp Bot ; 63(14): 5259-74, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22859678

RESUMEN

Ultraviolet radiation (UVR) induces damage in a variety of organisms, and cells may adapt by developing repair or tolerance mechanisms to counteract such damage; otherwise, the cellular fate is cell death. Here, the effect of UVR-induced cell damage and the associated signalling and repair mechanisms by which cells are able to survive was studied in Dunaliella tertiolecta. UVR did not cause cell death, as shown by the absence of SYTOX Green-positive labelling cells. Ultrastructure analysis by transmission electron microscopy demonstrated that the cells were alive but were subjected to morphological changes such as starch accumulation, chromatin disaggregation, and chloroplast degradation. This behaviour paralleled a decrease in F(v)/F(m) and the formation of cyclobutane-pyrimidine dimers, showing a 10-fold increase at the end of the time course. There was a high accumulation of the repressor of transcriptional gene silencing (ROS1), as well as the cell proliferation nuclear antigen (PCNA) in UVR-treated cells, revealing activation of DNA repair mechanisms. The degree of phosphorylation of c-Jun N-terminal kinase (JNK) and p38-like mitogen-activated protein kinases was higher in UVR-exposed cells; however, the opposite occurred with the phosphorylated extracellular signal-regulated kinase (ERK). This confirmed that both JNK and p38 need to be phosphorylated to trigger the stress response, as well as the fact that cell division is arrested when an ERK is dephosphorylated. In parallel, both DEVDase and WEHDase caspase-like enzymatic activities were active even though the cells were not dead, suggesting that these proteases must be considered within a wider frame of stress proteins, rather than specifically being involved in cell death in these organisms.


Asunto(s)
Daño del ADN/efectos de la radiación , Reparación del ADN , Rayos Ultravioleta/efectos adversos , Volvocida/efectos de la radiación , Proteínas Algáceas/metabolismo , Western Blotting , Caspasas/metabolismo , Citometría de Flujo , Fluorescencia , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Datos de Secuencia Molecular , Proteínas Nucleares/metabolismo , Fosforilación , Análisis de Secuencia de ADN , Volvocida/metabolismo
19.
Photochem Photobiol Sci ; 11(6): 1087-98, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22544332

RESUMEN

The combined effect of high solar ultraviolet radiation (UVR) and nutrient supply in a phytoplankton community of a high mountain lake is analyzed in a in situ experiment for 6 days with 2 × 2 factorial design. Interactive UVR × nutrient effects on structural and functional variables (algal biomass, chlorophyll a (chl a), primary production (PP), maximal electron transport rate (ETR(max)), and alkaline phosphatase activity (APA)), as well as stoichiometric ones (sestonic N per cell and N:P ratio) were found. Under non-nutrient enriched conditions, no deleterious effects of UVR on structural variables, PP, photosynthetic efficiency and ETR(max) were observed, whereas only particulate and total APA were affected by UVR. However, percentage excreted organic carbon (%EOC), dissolved APA and sestonic C and P per cell increased under UVR, leading to a decrease in algal C:P and N:P ratios. After nutrient enrichment, chl a, total algal biomass and PP were negatively affected by UVR whereas %EOC, ETR(max) and internal C, P and N content increased. We suggest that the mechanism of algal acclimation to UVR in this high UVR flux ecosystem seems to be related to the increase of internal algal P-content mediated by physiological mechanisms to save P and by a stimulatory UVR effect on dissolved extracellular APA. The mechanism involved in the unmasking effect of UVR after nutrient-enrichment may be the result of a greater sensitivity to UVR-induced cell damage, making the negative UVR effects more evident.


Asunto(s)
Fitoplancton/metabolismo , Rayos Ultravioleta , Fosfatasa Alcalina/metabolismo , Biomasa , Carbono/química , Carbono/metabolismo , Clorofila/análisis , Clorofila A , Ecosistema , Transporte de Electrón , Fluorometría , Alimentos , Lagos , Nitrógeno/química , Nitrógeno/metabolismo , Fósforo/química , Fósforo/metabolismo , Fitoplancton/enzimología , Fitoplancton/efectos de la radiación
20.
Food Sci Technol Int ; 18(3): 281-90, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22701061

RESUMEN

Polyunsaturated fatty acids play an important role in human nutrition, being associated with several health benefits. The analyzed vegetables, in spite of its low fat content, lower than 2%, present a high proportion of polyunsaturated fatty acids of n-3, n-6 and n-9 series, such as α-linolenic, linoleic and oleic acids, respectively. Wild edible plants contain in general a good balance of n-6 and n-3 fatty acids. The present study tries to contribute to the preservation and valorization of traditional food resources, studying the fatty acids profile of 20 wild vegetables by gas-liquid chromatography with flame ionization detection. Results show that species in which leaves are predominant in their edible parts have in general the highest polyunsaturated fatty acid/saturated fatty acid ratios: Rumex pulcher (5.44), Cichorium intybus (5.14) and Papaver rhoeas (5.00). Due to the low n-6/n-3 ratios of the majority of the samples, they can be considered interesting sources of n-3 fatty acids, especially those with higher total fat amount, such as Bryonia dioica, Chondrilla juncea or Montia fontana, with the highest contents of α-linolenic acid (67.78, 56.27 and 47.65%, respectively). The wild asparaguses of Asparagus acutifolius and Tamus communis stand out for their linoleic acid content (42.29 and 42.45%, respectively). All these features reinforce the interest of including wild plants in diet, as an alternative to the variety of vegetables normally used.


Asunto(s)
Ácidos Grasos Insaturados/química , Verduras/química , Análisis de los Alimentos , Valor Nutritivo , Hojas de la Planta/química , Tallos de la Planta/química , España
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