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1.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(2): 79-87, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35177367

RESUMO

Cardiogenic shock (CS) is a condition comprising multiple etiologies, which associates high mortality rates. Some scoring systems have been shown to be good predictors of hospital mortality in patients admitted to Critical Care Units (CCU). The main objective of this study is to analyze their usefulness and validity in a cohort of CS patients. METHODS: Observational unicentric study of a cohort of CS patients. SOFA, SAPS II and APACHE II scores were calculated in the first 24 h of CCU admission. RESULTS: 130 patients with CS were included. SOFA, SAPS II and APACHE II scores revealed good discrimination for hospital mortality: (AUC) ROC values (AUC: 0.711, 0.752 and 0.742 respectively; P = .6). Calibration, estimated by the Hosmer-Lemeshow test, was adequate in all cases. Acute coronary syndrome, lactate serum values, SAPS II score and vasoactive inotropic score (VIS) were found to be independent predictors for mortality, upon ICU admission. With these variables, a specific prognostic indicator was developed (SAPS-2-LIVE), which improved predictive capability for mortality in our series (AUC) ROC, 0.825 (95% CI 0.752-0.89). CONCLUSION: In this contemporary CS cohort, the aforementioned scores have been shown to have good predictive ability for hospital mortality. These findings could contribute to a more accurate risk stratification in CS.


Assuntos
Choque Cardiogênico , APACHE , Mortalidade Hospitalar , Humanos , Prognóstico , Estudos Retrospectivos , Choque Cardiogênico/diagnóstico
2.
Rev. esp. anestesiol. reanim ; 69(2): 79-87, Feb 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-206706

RESUMO

El shock cardiogénico (SC) es una entidad que comprende múltiples etiologías y asocia elevada mortalidad. Algunas escalas de gravedad han demostrado ser buenos predictores de mortalidad hospitalaria en pacientes ingresados en Unidades de Cuidados Intensivos (UCI). El objetivo principal de este estudio es analizar su utilidad y validez en una cohorte de pacientes en SC. Métodos: Estudio observacional unicéntrico. Se calcularon las escalas SOFA, SAPSII y APACHEII en las primeras 24horas de ingreso en UCI. Resultados: Se incluyeron 130 pacientes con SC. Las escalas SOFA, SAPSII y APACHEII mostraron buena discriminación para la mortalidad hospitalaria, obteniendo valores de área bajo la curva (AUC) ROC similares (AUC: 0,711, 0,752 y 0,742, respectivamente; p=0,6). La calibración, estimada por el test de Hosmer-Lemeshow, fue adecuada en todos los casos, SOFA (p=0,787), SAPSII (p=0,078) y APACHEII (p=0,522). Resultaron: predictores independientes de mortalidad intrahospitalaria: el síndrome coronario agudo (SCA), los valores de lactato sérico, el SAPSII y el índice de vasoactivos inotrópicos (VIS) en las primeras 24horas de ingreso en UCI.Con estas variables se desarrolló un indicador pronóstico específico para el SC (SAPS-2-LIVE) que mejora la capacidad predictiva de mortalidad en nuestra serie (AUC) ROC, 0,825 (IC 95% 0,752-0,89). Conclusión: En esta cohorte contemporánea de SC, las escalas SOFA, SAPSII y APACHEII han demostrado una buena capacidad de predicción de mortalidad hospitalaria. Estos hallazgos podrían contribuir a una mejor estratificación del riesgo en el SC.(AU)


Cardiogenic shock (CS) is a condition comprising multiple etiologies, which associates high mortality rates. Some scoring systems have been shown to be good predictors of hospital mortality in patients admitted to Critical Care Units (CCU). The main objective of this study is to analyze their usefulness and validity in a cohort of CS patients. Methods: Observational unicentric study of a cohort of CS patients. SOFA, SAPSII and APACHEII scores were calculated in the first 24hours of CCU admission. Results: 130 patients with CS were included. SOFA, SAPSII and APACHEII scores revealed good discrimination for hospital mortality: (AUC) ROC values (AUC: 0.711, 0.752 and 0.742 respectively; p=0.6). Calibration, estimated by the Hosmer-Lemeshow test, was adequate in all cases.Acute coronary syndrome, lactate serum values, SAPSII score and vasoactive inotropic score (VIS) were found to be independent predictors for mortality, upon ICU admission. With these variables, a specific prognostic indicator was developed (SAPS-2-LIVE), which improved predictive capability for mortality in our series (AUC) ROC, 0.825 (95% CI 0.752-0.89). Conclusion: In this contemporary CS cohort, the aforementioned scores have been shown to have good predictive ability for hospital mortality. These findings could contribute to a more accurate risk stratification in CS.(AU)


Assuntos
Humanos , Masculino , Índice de Gravidade de Doença , Mortalidade Hospitalar , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Pacientes Internados , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , APACHE , Anestesiologia , Reanimação Cardiopulmonar
3.
Case Rep Nephrol ; 2019: 2818074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236295

RESUMO

Allograft infiltration has been described in up to 20% of all patients with posttransplant lymphoproliferative disorder (PTLD), most representing EBV-positive B-cell lymphomas. Plasma cells are often observed in humoral rejection biopsies, but graft infiltration by plasmacytoma-like PTLD is rare. We report the case of a 54-year-old simultaneous pancreas-kidney transplant recipient (immunosuppression: OKT3, methylprednisolone, cyclosporine, and azathioprine), diagnosed with an IgG-kappa monoclonal gammopathy of undetermined significance eighteen years after transplant. Nine months later, pancreas allograft biopsy performed due to new-onset hyperglycemia (HgA1C 8.6%, C-peptide 6.15ng/mL and anti-GAD 0.9UI/mL) revealed a monotypic plasma cell infiltrate, CD19, CD79a, CD138 positive, with IgG-kappa light chain restriction, and EBV negative. PET-scan FDG uptake was limited to pancreas allograft. Tumor origin could not be established (using DNA microsatellite analysis). Despite treatment with bortezomib and dexamethasone, patient eventually died one month later. This is the first report of a late onset extramedullary plasmacytoma involving a pancreas allograft.

4.
Leukemia ; 32(3): 645-653, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28924241

RESUMO

Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases. CNA tended to be acquired early in the evolution of the disease and remained stable, whereas the mutational heterogeneity increased in a subset of tumors. The prognostic impact of different genes was related to the size of the mutated clone. Combining mutations and CNA, we observed that the accumulation of driver alterations (mutational complexity) gradually shortened the time to first treatment independently of the clonal architecture, IGHV status and Binet stage. Conversely, the overall survival was associated with the increasing subclonal diversity of the tumors but it was related to the age of patients, IGHV and TP53 status of the tumors. In conclusion, our study reveals that both the mutational complexity and subclonal diversity influence the evolution of CLL.


Assuntos
Biomarcadores Tumorais , Evolução Clonal/genética , Leucemia Linfocítica Crônica de Células B/genética , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Variações do Número de Cópias de DNA , Progressão da Doença , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Transdução de Sinais , Adulto Jovem
5.
Biofabrication ; 9(2): 025033, 2017 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-28393759

RESUMO

In this work a method for fabricating functionalized preclinical devices is presented. The manufacturing process combines a laser indirect writing technique to fabricate a soda-lime glass master and soft-lithography methods to obtain the final structure in polydimethylsiloxane (PDMS). The roughness of the device is modified in a controlled manner by applying a post-thermal treatment to the master, and thus devices with different roughness values are created. The PDMS devices are fully covered with human umbilical vein cells in a two-step process. In order to determine the most suitable device to perform bioassays, the cell attachment to the channel is evaluated with regards to the walls roughness when flow experiments are carried out.


Assuntos
Pesquisa Biomédica , Lasers , Modelos Cardiovasculares , Engenharia Tecidual , Materiais Biocompatíveis , Pesquisa Biomédica/instrumentação , Pesquisa Biomédica/métodos , Compostos de Cálcio , Células Cultivadas , Desenho de Equipamento , Células Endoteliais da Veia Umbilical Humana , Humanos , Óxidos , Hidróxido de Sódio , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
6.
Leukemia ; 29(3): 598-605, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25151957

RESUMO

Prospective identification of patients with chronic lymphocytic leukemia (CLL) destined to progress would greatly facilitate their clinical management. Recently, whole-genome DNA methylation analyses identified three clinicobiologic CLL subgroups with an epigenetic signature related to different normal B-cell counterparts. Here, we developed a clinically applicable method to identify these subgroups and to study their clinical relevance. Using a support vector machine approach, we built a prediction model using five epigenetic biomarkers that was able to classify CLL patients accurately into the three subgroups, namely naive B-cell-like, intermediate and memory B-cell-like CLL. DNA methylation was quantified by highly reproducible bisulfite pyrosequencing assays in two independent CLL series. In the initial series (n=211), the three subgroups showed differential levels of IGHV (immunoglobulin heavy-chain locus) mutation (P<0.001) and VH usage (P<0.03), as well as different clinical features and outcome in terms of time to first treatment (TTT) and overall survival (P<0.001). A multivariate Cox model showed that epigenetic classification was the strongest predictor of TTT (P<0.001) along with Binet stage (P<0.001). These findings were corroborated in a validation series (n=97). In this study, we developed a simple and robust method using epigenetic biomarkers to categorize CLLs into three subgroups with different clinicobiologic features and outcome.


Assuntos
Linfócitos B/metabolismo , Biomarcadores Tumorais/genética , Epigênese Genética , Cadeias Pesadas de Imunoglobulinas/genética , Leucemia Linfocítica Crônica de Células B/genética , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Linfócitos B/classificação , Linfócitos B/patologia , Metilação de DNA , Progressão da Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Máquina de Vetores de Suporte , Análise de Sobrevida , Tempo para o Tratamento , Resultado do Tratamento
7.
Leukemia ; 29(1): 96-106, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24781018

RESUMO

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), especially for the poor prognostic subgroup of NOTCH1-mutated patients. Here, we report that the γ-secretase inhibitor PF-03084014 inhibits the constitutive Notch activation and induces selective apoptosis in CLL cells carrying NOTCH1 mutations. Combination of PF-03084014 with fludarabine has a synergistic antileukemic effect in primary NOTCH1-mutated CLL cells, even in the presence of the protective stroma. At transcriptional level, PF-03084014 plus fludarabine treatment induces the upregulation of the proapoptotic gene HRK and the downmodulation of MMP9, IL32 and RAC2 genes that are related to invasion and chemotaxis. PF-03084014 also overcomes fludarabine-mediated activation of nuclear factor-κB signaling. Moreover, this combination impairs angiogenesis and CXCL12-induced responses in NOTCH1-mutated CLL cells, in particular those related to tumoral migration and invasion. Importantly, all these collaborative effects are specific for NOTCH1 mutation and do not occur in unmutated cases. In conclusion, we provide evidence that Notch is a therapeutic target in CLL cases with NOTCH1-activating mutations, supporting the use of Notch pathway inhibitors in combination with chemotherapy as a promising approach for the treatment of these high-risk CLL patients.


Assuntos
Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Leucemia Linfocítica Crônica de Células B/patologia , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica/prevenção & controle , Neovascularização Patológica/prevenção & controle , Receptor Notch1/genética , Tetra-Hidronaftalenos/farmacologia , Valina/análogos & derivados , Vidarabina/análogos & derivados , Idoso , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Mutação , Células Tumorais Cultivadas , Valina/farmacologia , Vidarabina/farmacologia
8.
Leukemia ; 27(5): 1100-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23295735

RESUMO

NOTCH1 has been found recurrently mutated in a subset of patients with chronic lymphocytic leukemia (CLL). To analyze biological features and clinical impact of NOTCH1 mutations in CLL, we sequenced this gene in 565 patients. NOTCH1 mutations, found in 63 patients (11%), were associated with unmutated IGHV, high expression of CD38 and ZAP-70, trisomy 12, advanced stage and elevated lactate dehydrogenase. Sequential analysis in 200 patients demonstrated acquisition of mutation in one case (0.5%) and disappearance after treatment in two. Binet A and B patients with NOTCH1-mutated had a shorter time to treatment. NOTCH1-mutated patients were more frequently refractory to therapy and showed shorter progression-free and overall survival after complete remission. Overall survival was shorter in NOTCH1-mutated patients, although not independently from IGHV. NOTCH1 mutation increased the risk of transformation to diffuse large B-cell lymphoma independently from IGHV, with this being validated in resampling tests of replicability. In summary, NOTCH1 mutational status, that was rarely acquired during the course of the disease, identify a genetic subgroup with high risk of transformation and poor outcome. This recently identified genetic subgroup of CLL patients deserves prospective studies to define their best management.


Assuntos
Leucemia Linfocítica Crônica de Células B/genética , Mutação , Receptor Notch1/genética , Transformação Celular Neoplásica , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Risco
9.
Blood Cells Mol Dis ; 49(3-4): 140-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22664374

RESUMO

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.


Assuntos
Proteínas de Ciclo Celular/genética , Disceratose Congênita/genética , Proteínas Nucleares/genética , Análise de Sequência de DNA/métodos , Telomerase/genética , Adolescente , Adulto , Medula Óssea/metabolismo , Medula Óssea/patologia , Criança , Pré-Escolar , Disceratose Congênita/diagnóstico , Disceratose Congênita/patologia , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Mutação , Desnaturação de Ácido Nucleico , Reação em Cadeia da Polimerase , Telômero/patologia , População Branca
10.
Leukemia ; 26(6): 1429-32, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22182921
11.
J Control Release ; 135(2): 119-26, 2009 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-19154763

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) has shown promise in the treatment of neurodegenerative disorders of basal ganglia origin such us Parkinson's disease (PD). In this study, we investigated the neurorestorative effect of controlled GDNF delivery using biodegradable microspheres in an animal model with partial dopaminergic lesion. Microspheres were loaded with N-glycosylated recombinant GDNF and prepared using the Total Recirculation One-Machine System (TROMS). GDNF-loaded microparticles were unilaterally injected into the rat striatum by stereotaxic surgery two weeks after a unilateral partial 6-OHDA nigrostriatal lesion. Animals were tested for amphetamine-induced rotational asymmetry at different times and were sacrificed two months after microsphere implantation for immunohistochemical analysis. The putative presence of serum IgG antibodies against rat glycosylated GDNF was analyzed for addressing safety issues. The results demonstrated that GDNF-loaded microspheres, improved the rotational behavior induced by amphetamine of the GDNF-treated animals together with an increase in the density of TH positive fibers at the striatal level. The developed GDNF-loaded microparticles proved to be suitable to release biologically active GDNF over up to 5 weeks in vivo. Furthermore, none of the animals developed antibodies against GDNF demonstrating the safety of glycosylated GDNF use.


Assuntos
Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Microesferas , Doença de Parkinson/terapia , Animais , Diferenciação Celular/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/química , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos adversos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/ultraestrutura , Glicosilação , Imuno-Histoquímica , Cinética , Ácido Láctico/química , Modelos Neurológicos , Células PC12 , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
12.
Eur J Pharm Biopharm ; 69(3): 844-51, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18417331

RESUMO

Glial cell-line derived neurotrophic factor (GDNF), a potent neurotrophic factor for dopaminergic neurons, appeared as a promising candidate for treating Parkinson's disease. GDNF microencapsulation could ensure protection against degradation due to the fragile nature of the protein. Poly(lactide-co-glycolide) (PLGA) microparticles loaded with recombinant glycosylated GDNF obtained in a mammalian cell line were prepared by TROMS, a semi-industrial technique capable of encapsulating fragile molecules maintaining their native properties. The effects of several parameters as PLGA copolymer type, PEG 400 quantity co-encapsulated with GDNF or drug loading, on the properties of the particles were investigated. Microparticles showed a mean diameter between 8 and 30 microm, compatible with their stereotaxic implantation. The drug entrapment efficiency ranged from 50.6% to 100% depending on the microsphere composition. GDNF was better encapsulated using hydrophilic polymers with high molecular weight such as RG 503H. In vitro drug release was influenced by the polymer type as well as by the amount of PEG 400 co-encapsulated with GDNF. Microparticles prepared using PLGA RG 503H released 67% of the total protein content within 40 days. Moreover, very low concentrations of poly(vinyl alcohol) were detected after microparticles washing and freeze-drying. Finally, a PC-12 bioassay demonstrated that the in vitro GDNF released was bioactive.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/administração & dosagem , Fator Neurotrófico Derivado de Linhagem de Célula Glial/química , Animais , Biotransformação , Preparações de Ação Retardada , Composição de Medicamentos , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Excipientes , Fator Neurotrófico Derivado de Linhagem de Célula Glial/isolamento & purificação , Cinética , Ácido Láctico , Microesferas , Células PC12 , Tamanho da Partícula , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Solubilidade
13.
Int J Pharm ; 344(1-2): 9-15, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17499462

RESUMO

Glial cell line-derived neurotrophic factor (GDNF) neuroprotective effect on dopaminergic neurons has been described in vitro and in vivo, turning up as a promising drug for the treatment of Parkinson's disease. Unglycosylated bacteria-obtained GDNF has already been successfully delivered for a long period of time through an infusion pump directly to the putamen of Parkinsonian patients. Nevertheless, improved distribution and safety issues need to be solved and alternative strategies to long-term delivery seem necessary. The use of glycosylated GDNF could eliminate some safety concerns regarding the presence of antibodies against exogenous unglycosylated GDNF used for the treatment. Therefore, we have chosen a mammalian expression system as a source of glycosylated GDNF. In the present work, we describe the purification of recombinant rat GDNF from the culture media of baby hamster kidney (BHK) cells through several purification steps. Highly pure N-glycosylated recombinant GDNF has been obtained similar to the endogenous protein. Furthermore, the purified protein is biologically active when tested its ability to induce PC12 neurite outgrowth.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/isolamento & purificação , Animais , Linhagem Celular , Células Cultivadas , Cricetinae , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Glicosilação , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Ratos , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia
14.
An. sist. sanit. Navar ; 29(3): 325-335, sept.-dic. 2006. ilus
Artigo em Es | IBECS | ID: ibc-052250

RESUMO

La enfermedad de Parkinson es la segunda enfermedad neurodegenerativa más común después del Alzheimer. Actualmente se dispone únicamente de terapias sintomáticas que, aunque son muy eficaces en las primeras etapas de la enfermedad poseen a largo plazo considerables efectos secundarios. La terapia ideal sería aquella que permitiese frenar o detener la progresión de la enfermedad. Este es el caso de las terapias neuroprotectoras y neurorestauradoras. De entre todas ellas, la terapia celular y la terapia con factores tróficos tipo GDNF son las que mayores expectativas han generado en la comunidad científica. Aunque ya se ha planteado el uso de GDNF para el tratamiento de la enfermedad de Parkinson, es necesario buscar nuevas estrategias que permitan administrar dicho factor neurotrófico en las zonas concretas del cerebro donde vaya a ejercer su acción. Aquí se discute el uso de micropartículas como el sistema más apropiado para la administración de dicho factor neurotrófico


Parkinson´s disease is the second most common neurodegenerative disorder after Alzheimer´s disease. Current therapies are symptomatic and, although these therapies are efficacious during the early stages of the disease, they present important side effects when they are used for a long time. The ideal therapy would be the one that would slow down or stop the progression of the disease. This can be achieved, for instance, with neuroprotective and neurorestorative therapies. Among them, cell therapy and therapy with trophic factors such as glial cell line derived neurotrophic factor (GDNF) are the most challenging and promising ones for the scientific community. Although the use of GDNF as a treatment for Parkinson ´s disease was proposed several years ago, it is necessary to develop alternative strategies to deliver GDNF appropriately to concrete areas of the brain. Here, the use of microspheres as the most suitable tool for the administration of this neurotrophic factor is discussed


Assuntos
Humanos , Doença de Parkinson/terapia , Fármacos Neuroprotetores/administração & dosagem , Di-Hidroxifenilalanina/farmacocinética , Terapia Baseada em Transplante de Células e Tecidos/métodos , Ubiquinona/farmacocinética , Fatores de Crescimento Neural/uso terapêutico
15.
Neurologia ; 21(4): 181-7, 2006 May.
Artigo em Espanhol | MEDLINE | ID: mdl-16832772

RESUMO

INTRODUCTION: The Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a health-related quality of life specific questionnaire for multiple sclerosis (MS) patients. The objective of this study was to develop the Spanish version of the MSQOL-54 and to obtain a conceptually equivalent version to the original one for its use in patients with MS in the first phase of the project. METHODS: A transcultural adaptation procedure was designed according to the following phases: a) two independent translations made by bilingual native Spanish speaking translators (forward translation); b) a revision of the items by an expert panel; c) a back translation by a bilingual native English speaking person; d) comparison with the original version (expert panel and advise by the original authors), and e) cognitive debriefing (interviews with subjects with MS) to test the comprehension and feasibility of the instrument. RESULTS: Ten interviews were carried out with 5 men and 5 women with MS, aged 21 to 54 years, with different education levels and EDSS scores ranging from 1,0 to 8,0. Most of the patients found the questionnaire easy to fill out and the understanding favorable. Only one item (item 51) was modified after the cognitive debriefing to improve its comprehension. Finally, a final pretest version was obtained. CONCLUSIONS: The procedure carried out maximizes the conceptual equivalence between the original MSQOL-54 and the translated version and shows that the Spanish pre-test version is comprehensible and its administration feasible in patients with MS. The psychometric properties must be evaluated in the next phase of the project.


Assuntos
Esclerose Múltipla/psicologia , Qualidade de Vida , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia
16.
Neurología (Barc., Ed. impr.) ; 21(4): 181-187, mayo 2006. tab, graf
Artigo em Es | IBECS | ID: ibc-048785

RESUMO

Introducción. El Multiple Sclerosis Quality of Life 54 (MSQOL-54) es un cuestionario de calidad de vida relacionada con la salud especifico para esclerosis múltiple (EM). El objetivo de este estudio fue desarrollar la versión española del MSQOL-54 y obtener en una primera fase una versión conceptualmente equivalente a la original para su uso en pacientes con EM. Métodos. Se diseñó un proceso de adaptación transcultural con las siguientes etapas: a) traducción independiente por dos traductores bilingües de lengua materna española; b) revisión de los ítems por un panel de expertos; e) traducción inversa por una persona bilingüe de lengua materna inglesa; d) comparación eon la versión original (panel de expertos y asesoramiento de los autores originales), y e) entrevistas individuales a pacientes con EM para valorar la comprensión y factibilidad del instrumento (cognitive debriefing). Resultados. Se realizaron 10 entrevistas a 5 hombres y 5 mujeres con EM, de 21 a 54 años, con diferentes niveles educativos y diversos grados de discapacidad física (Expanded Disability Status Scale, 1.0-8.0). A la mayoría de pacientes les pareció sencilla la cumplimentación y fácil la comprensión. Sólo uno de los ítems (item 51) fue modificado después de la prueba para mejorar su comprensión. Finalmente se obtuvo la versión final pretest. Conclusiones. El proceso seguido maximiza la equivalencia conceptual con el MSQOL-54 original y muestra que la versión pretest española es comprensible y su administración factible en los pacientes con EM. Las propiedades métricas serán evaluadas en la siguiente fase del proyecto


Introduction: The Multiple Sclerosis Quality of Life 54 (MSQOL-54) is a health-related quality of life specific questionnaire for multiple sclerosis (MS) patients. The objective of this study was to develop the Spanish version of the MSQOL-54 and to obtain a conceptually equivalent version to the original one for its use in patients with MS in the first phase of the project. Methods: A transcultural adaptation procedure was designed according to the following phases: a) two independent translations made by bilingual native Spanish speaking translators (forward translation); b) a revision of the items by an expert panel; c) a back translation by a bilingual native English speaking person; d) comparison with the original version (expert panel and advise by the original authors), and e) cognitive debriefing (interviews with subjects with MS) to test the comprehension and feasibility of the instrument. Results: Ten interviews were carried out with 5 men and 5 women with MS, aged 21 to 54 years, with different education levels and EDSS scores ranging from 1,0 to 8,0. Most of the patients found the questionnaire easy to fill out and the understanding favorable. Only one item (item 51) was modified after the cognitive debriefing to improve its comprehension. Finally, a final pretest version was obtained. Conclusions: The procedure carried out maximizes the conceptual equivalence between the original MSQOL-54 and the translated version and shows that the Spanish pre-test version is comprehensible and its administration feasible in patients with MS. The psychometric properties must be evaluated in the next phase of the project


Assuntos
Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Humanos , Esclerose Múltipla/psicologia , Qualidade de Vida , Inquéritos e Questionários , Atividades Cotidianas , Esclerose Múltipla/fisiopatologia
17.
Eur J Neurosci ; 23(8): 2099-108, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16630057

RESUMO

The position of the caudal intralaminar nuclei within basal ganglia circuitry has largely been neglected in most studies dealing with basal ganglia function. During the past few years, there has been a growing body of evidence suggesting that the thalamic parafascicular nucleus in rodents (PF) exerts a multifaceted modulation of basal ganglia nuclei, at different levels. Our aim was to study the activity of the thalamostriatal pathway in rats with unilateral dopaminergic depletion. The experimental approach comprised first unilateral delivery of 6-OHDA in the medial forebrain bundle. Thirty days post-lesioning, animals showing a clear asymmetry were then subjected to bilateral injection of Fluoro-Gold (FG) within the striatum. Subsequently, expression of the mRNA encoding the vesicular glutamate transporter 2 (vGLUT2) was detected within thalamostriatal-projecting neurons (FG-labeled) by in situ hybridization and the results were confirmed by laser-guided capture microdissection microscopy followed by real-time PCR. The data showed that there was a marked neuronal loss restricted to PF neurons projecting to the dopamine-depleted striatum. Moreover, PF neurons innervating the dopamine-depleted striatum were intensely hyperactive. These neurons showed a marked increase on the expression of vGLUT2 mRNA as well as for the mRNA encoding the subunit I of cytochrome oxidase as compared with those neurons projecting to the striatum with normal dopamine content. Thus, the selective neurodegeneration of PF neurons innervating the striatum together with the increased activity of the thalamostriatal pathway coexist after nigrostriatal denervation.


Assuntos
Denervação , Lateralidade Funcional/fisiologia , Neostriado/fisiologia , Vias Neurais/fisiologia , Substância Negra/fisiologia , Tálamo/fisiologia , Animais , Comportamento Animal , Contagem de Células/métodos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Hibridização In Situ/métodos , Masculino , Atividade Motora/fisiologia , Vias Neurais/lesões , Oxidopamina/efeitos adversos , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Teste de Desempenho do Rota-Rod/métodos , Estilbamidinas/farmacocinética , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/genética , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo
18.
Bone Marrow Transplant ; 37(9): 873-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16547488

RESUMO

Dendritic cells (DC) play a key role in initiating immune reactions after allogeneic stem cell transplantation. The two main peripheral blood DC populations are myeloid (DC1) and lymphoplasmacytoid (DC2). A new subset of myeloid DC, expressing CD16, has been identified. We analyzed the number and CD86 expression of DC subsets in peripheral blood of 18 healthy donors, before and after granulocyte colony-stimulating factor (G-CSF) and in the inoculum of allogeneic peripheral blood transplants (allo-PBT; n=100) and allogeneic bone marrow transplants (allo-BMT; n=22). Granulocyte colony-stimulating factor administration increased the median number of DC1 (P=0.0007), of DC2 (P<0.0001) and of DC CD16+ (P=0.0001). Granulocyte colony-stimulating factor administration was also associated with a significant decrease of CD86 expression on DC1 (P=0.0003) and with a trend for an increase on DC CD16+ (P=0.07). Recipients of allo-PBT received similar quantities of DC1 and higher doses of DC2 and DC CD16+ than recipients of allo-BMT (P=0.5; P=0.0001; P<0.0001, respectively). Granulocyte colony-stimulating factor modifies the number of DC in peripheral blood and the expression of the costimulatory molecule CD86. This resulted in a different composition of DC2 and especially of DC CD16+ in the harvests, which might explain some of the differences observed in allogeneic reactions after allo-PBT with respect to allo-BMT.


Assuntos
Antígeno B7-2/genética , Transplante de Medula Óssea/imunologia , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Anticorpos Monoclonais , Antígenos CD/sangue , Antígenos CD/genética , Transplante de Medula Óssea/patologia , Células Dendríticas/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunofenotipagem , Ativação Linfocitária , Subpopulações de Linfócitos/imunologia , Receptores de IgG/sangue , Doadores de Tecidos , Transplante Homólogo/imunologia
19.
Aten Primaria ; 37(4): 203-8, 2006 Mar 15.
Artigo em Espanhol | MEDLINE | ID: mdl-16545264

RESUMO

OBJECTIVE: To assess the psychometric properties of the Spanish version of the Vecú et Santé Perçue de l'Adolescent (VSP-A) in terms of reliability and validity. DESIGN: Cross-sectional study. SETTING: Pilot study parallel to the European Kidscreen project. Two secondary schools, one public and one private, were selected for their suitability in Barcelona and Gerona (Catalonia, Spain). The sample unit was the classroom. PARTICIPANTS: A sample of 354 adolescents aged 12 to 18 years old was selected. MAIN MEASUREMENTS: The Spanish VSP-A questionnaire was administered, and again a week later to check its test-retest stability. The KINDL questionnaire was administered in parallel. RESULTS: The response rate was 82% (n=291). The Spanish version of the VSP-A showed good internal consistency and acceptable test-retest reliability (Cronbach's alpha: 0.69-0.92, intraclass correlation coefficient [ICC]: 0.69-0.74) in most domains. Domains measuring a similar concept in the VSP-A and KINDL had closer correlation coefficients than those measuring different constructs (P<.05), which demonstrates its convergent validity. Girls had worse self-perceived health than boys (lower vitality, physical and emotional well-being and self-esteem, and a lower general score on the VSP-A; p<.01). These differences were more obvious in older teens (16-18 years old). CONCLUSIONS: The Spanish VSP-A showed good psychometric properties and results were consistent with the original French version. The results mean we have an adequate HRQL instrument for teens and for use in primary care and public health.


Assuntos
Nível de Saúde , Qualidade de Vida , Inquéritos e Questionários , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Projetos Piloto , Reprodutibilidade dos Testes
20.
Aten. prim. (Barc., Ed. impr.) ; 37(4): 203-208, mar. 2006. ilus, tab
Artigo em Es | IBECS | ID: ibc-045828

RESUMO

Objetivo. Evaluar las propiedades psicométricas de la versión española del Vecú et Santé Perçue de l'Adolescent (VSP-A) en términos de fiabilidad y validez. Diseño. Estudio transversal. Emplazamiento. Estudio piloto paralelo al proyecto europeo Kidscreen. Se seleccionaron por conveniencia 2 colegios de enseñanza secundaria (ESO, bachillerato y ciclos formativos) y de titularidad pública y privada en Barcelona y Gerona. La unidad muestral fue el aula. Participantes. Se seleccionaron 354 adolescentes entre 12 y 18 años. Mediciones principales. Se administró la versión española del VSP-A. Se volvió a administrar 1 semana después para analizar su estabilidad (test-retest). De forma paralela se administró el cuestionario KINDL. Resultados. La proporción de respuesta obtenida fue del 82% (n = 291). La versión española del VSP-A presentó una consistencia interna y una estabilidad test-retest aceptables (* de Cronbach, 0,69-0,92 y coeficiente de correlación intraclase, 0,69-0,74) en la mayoría de sus dimensiones. Las dimensiones del VSP-A que miden un constructo similar a las del KINDL presentaron correlaciones más elevadas que las dimensiones que miden constructos diferentes (p < 0,05), lo que apoya su validez convergente. Las chicas presentaron peor salud percibida que los chicos (menos energía, bienestar emocional, bienestar físico y autoestima y una puntuación global en el VSP-A más baja; p < 0,01). Estas diferencias fueron más evidentes en los de más edad (16-18 años). Conclusiones. La versión española del VSP-A ha mostrado buenas propiedades psicométricas. Los resultados son consistentes en la versión original francesa y permiten disponer de un instrumento de calidad de vida relacionada con la salud para adolescentes adecuado para uso en atención primaria y salud pública


Objective. To assess the psychometric properties of the Spanish version of the Vecú et Santé Perçue de l'Adolescent (VSP-A) in terms of reliability and validity. Design. Cross-sectional study. Setting. Pilot study parallel to the European Kidscreen project. Two secondary schools, one public and one private, were selected for their suitability in Barcelona and Gerona (Catalonia, Spain). The sample unit was the classroom. Participants. A sample of 354 adolescents aged 12 to 18 years old was selected. Main measurements. The Spanish VSP-A questionnaire was administered, and again a week later to check its test-retest stability. The KINDL questionnaire was administered in parallel. Results. The response rate was 82% (n=291). The Spanish version of the VSP-A showed good internal consistency and acceptable test-retest reliability (Cronbach's *: 0.69-0.92, intraclass correlation coefficient [ICC]: 0.69-0.74) in most domains. Domains measuring a similar concept in the VSP-A and KINDL had closer correlation coefficients than those measuring different constructs (P<.05), which demonstrates its convergent validity. Girls had worse self-perceived health than boys (lower vitality, physical and emotional well-being and self-esteem, and a lower general score on the VSP-A; P<.01). These differences were more obvious in older teens (16-18 years old). Conclusions. The Spanish VSP-A showed good psychometric properties and results were consistent with the original French version. The results mean we have an adequate HRQL instrument for teens and for use in primary care and public health


Assuntos
Masculino , Feminino , Adolescente , Humanos , Qualidade de Vida , Psicometria/instrumentação , Nível de Saúde , Qualidade de Vida , Estudos Transversais , Desenvolvimento do Adolescente
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