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1.
Int. microbiol ; 22(2): 169-179, jun. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-184824

RESUMO

Oxysterol-binding protein is an important non-vesicular trafficking protein involved in the transportation of lipids in eukaryotic cells. Oxysterol-binding protein is identified as oxysterol-binding protein-related proteins (ORPs) in mammals and oxysterol-binding protein homologue (Osh) in yeast. Research has described the function and structure of oxysterol-binding protein in mammals and yeast, but little information about the protein's structure and function in filamentous fungi has been reported. This article focuses on recent advances in the research of Osh proteins in yeast and filamentous fungi, such as Aspergillus oryzae, Aspergillus nidulans, and Candida albicans. Furthermore, we point out some problems in the field, summarizing the membrane contact sites (MCS) of Osh proteins in yeast, and consider the future of Osh protein development


No disponible


Assuntos
Fungos/genética , Receptores de Esteroides/genética , Leveduras/genética , Proteínas de Transporte/genética , Proteínas Fúngicas/genética , Fungos/metabolismo , Receptores de Esteroides/metabolismo , Leveduras/metabolismo , Proteínas de Transporte/metabolismo , Proteínas Fúngicas/metabolismo , Fungos/química , Metabolismo dos Lipídeos , Domínios Proteicos , Receptores de Esteroides/química , Leveduras/química
2.
Rev. esp. enferm. dig ; 111(4): 294-300, abr. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-189926

RESUMO

Antecedentes: se ha propuesto que el sobrecrecimiento bacteriano del intestino delgado (SBID) y la traslocación bacteriana a través de la pared intestinal se relacionan con el hígado graso no alcohólico (HGNA). El objetivo del presente estudio ha sido estudiar dicha relación en obesos mórbidos. Pacientes y métodos: se incluyeron consecutivamente pacientes con obesidad mórbida previo a su intervención de cirugía bariátrica. Los criterios de exclusión fueron: biopsia hepática normal, otras causas de enfermedad hepática o atrofia de la mucosa duodenal. Se realizó una gastroscopia para cultivo del aspirado duodenal, biopsias duodenales y extracción de sangre venosa periférica para estudio de lipopolisacárido (LPS) y proteína de unión del LPS (LBP). La biopsia hepática se realizó durante la intervención quirúrgica. Resultados: se incluyeron 71 pacientes; 26 fueron excluidos por biopsia hepática normal. Cuarenta y cinco tenían HGNA. Dieciocho eran varones, con edad media de 45,8 años (22-69) e índice de masa corporal (IMC) de 47,8 kg/m2 (37-58); el 25% tuvo SBID en el cultivo del aspirado duodenal. Existió significación estadística entre niveles de LBP y SBID con el grado de esteatosis (p < 0,05 y p = 0,077, respectivamente). No existió relación estadística con el índice de esteatohepatitis no alcohólica (EHNA), aunque sí hubo una tendencia a su asociación. Los niveles de LPS no guardaron relación con el grado de esteatosis o el índice de EHNA. Conclusiones: en pacientes con obesidad mórbida e HGNA se observan mayores niveles circulantes de LBP y mayor frecuencia de SBID cuanto mayor es el grado de esteatosis hepática


Background: small intestinal bacterial overgrowth (SIBO) and bacterial translocation across the intestinal wall have been allegedly associated with non-alcoholic fatty liver (NAFL). Our goal was to study such alleged association in morbidly obese patients. Patients and methods: patients with morbid obesity were consecutively included prior to bariatric surgery. Exclusion criteria included normal liver biopsy, other causes of liver disease, and duodenal mucosal atrophy. A gastroscopy was performed for duodenal aspirate culture and duodenal biopsy, and peripheral venous blood was drawn to assess lipopolysaccharide (LPS) and LPS-binding protein (LBP) levels. A liver biopsy was carried out during surgery. Results: seventy-one patients were included; 26 were excluded because of normal liver biopsy. Forty-five had NAFL. Eighteen were male, mean age was 45.8 years (22-69), and BMI was 47.8 kg/m2 (37-58). A total of 25% had SIBO in their duodenal aspirate culture. There was statistical significance for the association of LBP levels and SIBO with steatosis grade (p < 0.05 and p = 0.077, respectively). There was no statistical association with non-alcoholic steatohepatitis (NASH) index, but a trend towards association was found. LPS levels were not associated with steatosis grade or NASH index. Conclusions: the higher the grade of liver steatosis, the higher were the circulating LBP levels and SIBO rates seen in patients with morbid obesity and NAFL


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Fígado Gorduroso/microbiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Obesidade Mórbida/microbiologia , Translocação Bacteriana/fisiologia , Proteínas da Fase Aguda/análise , Biomarcadores/análise , Estudos Transversais , Proteínas de Transporte/análise , Lipopolissacarídeos/análise , Estudos Prospectivos , Síndrome Metabólica/fisiopatologia
4.
Allergol. immunopatol ; 46(6): 565-570, nov.-dic. 2018. tab
Artigo em Inglês | IBECS | ID: ibc-177896

RESUMO

Introduction: Lipid transfer proteins (LTPs) are panallergens found in many plant foods. They are a common cause of food-induced anaphylaxis (FIA) in adults living in the Mediterranean area. LTPs have also been proposed as a main cause of food-dependent exercise-induced anaphylaxis (FDEIA). Objectives: Describe clinical characteristics and allergen sensitization profiles in patients with FIA related to LTP. Materials and Methods: Forty-three patients were included, aged 3-52 years with a clinical history of FIA and proven sensitization to LTP. Patients were tested with a multiple plant food and pollen panel and specific IgE to LTP allergens. LTP sensitization was assessed by in vivo (Pru p 3, LTP extract) and/or by in vitro tests (specific IgE, ImmunoCAP/ISAC(R)). Results: Median age of first anaphylactic episode was 24 years (range 2-51), 44% had asthma, 74% were atopic and 42% had pollinosis (olive, mugwort, plane tree, wall pellitory and cypress). Co-sensitization to profilins was found in 22%. Overall in our center, LTP-induced anaphylaxis represents 17% of all causes of FIA. Foods implicated in anaphylactic reactions were: fresh fruits 51%, tree nuts 42%, vegetables (including peanut) 40% and seeds 14%. Seven patients had FDEIA. Conclusions: LTPs are important allergens of FIA in Portugal. Clinical reactivity to several taxonomically unrelated plant foods may raise suspicion toward LTP sensitization. The association of LTP-induced anaphylaxis with pollinosis is relevant in our country. The unpredictable clinical expression depends on the effect of cofactors such as exercise. The management of avoidance plans can be challenging due to LTP being a widely cross-reacting allergen in plant foods


No disponible


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Anafilaxia/epidemiologia , Antígenos de Plantas/imunologia , Proteínas de Transporte/imunologia , Hipersensibilidade Alimentar/epidemiologia , Proteínas de Plantas/imunologia , Reações Cruzadas , Imunização , Imunoglobulina E/metabolismo , Portugal/epidemiologia , Síndrome
5.
Rev. neurol. (Ed. impr.) ; 67(12): 491-504, 16 dic., 2018. ilus
Artigo em Espanhol | IBECS | ID: ibc-175179

RESUMO

Introducción. Los aminoácidos glutamato y glicina, aparte de su papel en la síntesis de proteínas, son dos neurotransmisores fundamentales en el sistema nervioso central de los mamíferos. El primero es ubicuo y está implicado en vías excitatorias de la neocorteza, la retina y el cerebelo, y el segundo está asociado a vías inhibitorias de zonas caudales del cerebro. Sin embargo, ambos comparten su manera de actuar al integrarse en el funcionamiento de los receptores de glutamato del tipo NMDA, fundamentales en la regulación de sistemas motores, sensitivos y cognitivos. Objetivo. Evidenciar la necesidad de una regulación exquisita de las concentraciones de glutamato y de glicina en los espacios intra y extracelulares del sistema nervioso mediante la actuación de transportadores muy específicos para ambos neurotransmisores localizados en la membrana plasmática de las neuronas y de las células de la glía. Desarrollo. Se describe el papel de los transportadores de glutamato y glicina en la neurotransmisión glutamatérgica y glicinérgica, y en el funcionamiento del sistema nervioso. Se señalan las consecuencias patológicas de los desequilibrios en estas vías de señalización. También se describe su participación en patologías como la esquizofrenia, el dolor crónico, la isquemia cerebral, la hiperplexia hereditaria, la hiperglicinemia no cetósica o trastornos neurodegenerativos. Conclusiones. El conocimiento de la forma molecular de actuar de los transportadores de glutamato y de glicina está permitiendo la identificación y el desarrollo de nuevas estrategias terapéuticas para patologías como las descritas y el desarrollo de nuevos fármacos


Introduction. The amino acids glutamate and glycine, apart from their role in protein synthesis, are two fundamental neurotransmitters in the central nervous system of mammals. The first one is ubiquitous and is involved in excitatory pathways of the neocortex, the retina and the cerebellum, and the second is involved in inhibitory pathways of brain caudal areas. However, both share their way of acting by integrating into the functioning of glutamate receptors of the NMDA type fundamentals in the regulation of motor, sensory and cognitive systems. Aim. To highlight the need for a fine regulation of glutamate and glycine concentrations in the intracellular and extracellular spaces of the nervous system through the action of very specific transporters for both neurotransmitters located in the plasma membrane of neurons and glial cells. Development. The role of the glutamate and glycine transporters in glutamatergic and glycinergic neurotransmission and in the functioning of the nervous system is described. The pathological consequences of imbalances in these signaling pathways are pointed out. We also describe its involvement in pathologies such as schizophrenia, chronic pain, cerebral ischemia, diseases such as hereditary hyperekplexia and the non-ketotic hyperglycinemia, and neurodegenerative disorders. Conclusions. The knowledge at molecular level of the way of acting of these transporters for glutamate and glycine is allowing the identification and development of new therapeutic strategies for pathologies such as those described above and the development of new drugs


Assuntos
Humanos , Ácido Glutâmico , Glicina/metabolismo , Sistema Nervoso Central/metabolismo , Proteínas de Transporte/metabolismo , Esquizofrenia/metabolismo , Dor Crônica/metabolismo , Isquemia Encefálica/metabolismo , Hiperglicinemia não Cetótica/metabolismo , Doenças Neurodegenerativas/metabolismo , Esquizofrenia/fisiopatologia , Dor Crônica/fisiopatologia , Isquemia Encefálica/fisiopatologia , Hiperglicinemia não Cetótica , Doenças Neurodegenerativas/fisiopatologia
6.
Allergol. immunopatol ; 46(5): 482-490, sept.-oct. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-177884

RESUMO

Background: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. Methods: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). Results: Peach-allergic patients (n = 27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n = 17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P < 0.05). Conclusions: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/diagnóstico , Imunoglobulina E/sangue , Prunus persica/efeitos adversos , Antígenos de Plantas/efeitos adversos , Proteínas de Transporte/efeitos adversos , Proteínas de Transporte/imunologia , Ensaio de Imunoadsorção Enzimática , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/imunologia , Giberelinas/administração & dosagem , Giberelinas/efeitos adversos , Giberelinas/imunologia , Proteínas Recombinantes
7.
Nefrología (Madr.) ; 36(6): 637-642, nov.-dic. 2016. ilus, tab, graf
Artigo em Espanhol | IBECS | ID: ibc-158753

RESUMO

La enfermedad renal crónica tiene mayor riesgo de eventos cardiovasculares. En los últimos años, han ido adquiriendo mayor importancia las toxinas unidas a proteínas, que han sido asociadas a mayor morbimortalidad y que se caracterizan por la dificultad para su depuración en diálisis. El objetivo de este estudio es valorar la influencia de altos volúmenes convectivos en HDF-OL posdilucional sobre la eliminación de medianas moléculas, pequeñas moléculas y moléculas unidas a proteínas. Material y métodos: Se realizaron 40 sesiones de HDF-OL posdilucional en 13 pacientes y se midió el porcentaje de reducción de toxinas de distinto peso molecular y entre ellas, moléculas unidas a proteínas como el p-cresyl sulfato, indoxyl sulfato y homocisteína. Resultados: El volumen convectivo total fue de 28,3(5,1) litros con un rango entre 16,3 y 38,0 litros. La reducción media de moléculas unidas a proteínas fue de 44,4 (15,7) % para el p-cresyl sulfato, de 48,7(14,1) % para el indoxyl sulfato y de 58,6(8,8) % para la homocisteína. Además, se encontró una relación directa y estadísticamente significativa entre el porcentaje de reducción de las tres moléculas con el volumen de sustitución y con el Kt/V. Conclusión: Altos volúmenes convectivos totales en HDF-OL en posdilución se asocian a una mayor eliminación de toxinas urémicas unidas a proteínas (AU)


Chronic kidney disease is associated with an increased risk of cardiovascular events. In recent years, protein-bound toxins have become more important due to their association with increased morbidity and mortality, characterised by inadequate clearance during dialysis. The purpose of this study is to assess the influence of high convective volumes on postdilution online haemodiafiltration (OL-HDF) on the removal of medium-sized molecules, small molecules and protein-bound molecules. Material and methods: In forty postdilutional OL-HDF sessions, the reduction rates of toxins of different molecular weights were measured in 13 patients, including protein-bound molecules such as p-cresyl sulphate, indoxyl sulphate and homocysteine. Results: Total convective volume was 28.3 (5.1) litres (range 16.3-38.0 litres). Mean reduction rate of protein-bound molecules was 44.4% (15.7%), 48.7% (14.1%) and 58.6% (8.8%) for p-cresyl sulphate, indoxyl sulphate and homocysteine, respectively. Moreover, a statistically significant direct association was found between the reduction rates of all three molecules, the replacement volume and the Kt/V. Conclusion: High convective volumes during postdilution OL-HDF are associated with increased removal of protein-bound uraemic toxins (AU)


Assuntos
Humanos , Insuficiência Renal Crônica/fisiopatologia , Terapia de Substituição Renal/estatística & dados numéricos , Hemodiafiltração/estatística & dados numéricos , Homocisteína/isolamento & purificação , Resultado do Tratamento , Proteínas de Transporte/análise , Insuficiência Renal Crônica/terapia
8.
J. physiol. biochem ; 72(3): 485-494, sept. 2016. tab, graf
Artigo em Inglês | IBECS | ID: ibc-168290

RESUMO

The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fatty acids (PUFAs) are known to induce on hepatic de novo lipogenesis (DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fatty acids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 % w/w) diets (HFDs) enriched in saturated fatty acids (SFAs) or unsaturated fatty acids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fatty acid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect (AU)


No disponible


Assuntos
Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Lipídeos/sangue , Lipogênese , Fígado/metabolismo , Proteínas de Transporte/antagonistas & inibidores , Hipertrigliceridemia/prevenção & controle , Gorduras Insaturadas na Dieta/uso terapêutico , Ratos Wistar , Fatores de Tempo , Triglicerídeos , Fosfolipídeos/metabolismo , Ácidos Graxos Insaturados , Ácidos Graxos Monoinsaturados , Mitocôndrias Hepáticas , Ácido Graxo Sintases , Acetil-CoA Carboxilase
9.
Rev. esp. enferm. dig ; 107(11): 672-676, nov. 2015. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-145295

RESUMO

Antecedentes: las proteínas de unión estrecha (UE) regulan la permeabilidad paracelular. La permeabilidad intestinal puede estar modulada por la microbiota comensal. Las manipulaciones de la microbiota intestinal con antibióticos como la bacitracina y neomicina han resultado ser útiles para el tratamiento de la diarrea inducida por Clostridium difficile o los fármacos quimioterápicos. Objetivos: evaluar los efectos de la depleción de la microbiota mediante la administración oral de bacitracina y neomicina sobre la permeabilidad intestinal y la expresión de las proteínas de UE en ratón. Métodos: los ratones recibieron por vía oral la combinación de neomicina y bacitracina durante 7 días. La permeabilidad intestinal se cuantificó con el método del dextrano marcado con isotiocianato de fluoresceína (FITC-dextrano). La expresión de las proteínas de UE en el intestino se determinó mediante PCR a tiempo real. Resultados: los niveles de FITC-dextrano en suero se redujeron a la mitad en los ratones tratados con antibióticos, indicando una reducción de la permeabilidad intestinal. Los antibióticos incrementaron la expresión de zónula occludens 1 (ZO- 1), molécula de adhesión de unión A (JAM-A) y ocludina en íleon y de ZO-1, claudina-3 y claudina-4 en colon. Conclusiones: la combinación de neomicina y bacitracina reduce la permeabilidad intestinal e incrementa la expresión de ZO-1, JAM-A y ocludina en íleon y ZO-1, claudina-3 y claudina-4 en colon (AU)


Background: Tight-junction (TJ) proteins regulate paracellular permeability. Gut permeability can be modulated by commensal microbiota. Manipulation of the gut microbiota with antibiotics like bacitracin and neomycin turned out to be useful for the treatment of diarrhoea induced by Clostridium difficile or chemotherapy drugs. Aim: To evaluate the effects of the microbiota depletion evoked by the oral administration of neomycin and bacitracin on the intestinal permeability and expression of TJ proteins in mice. Methods: Mice received neomycin and bacitracin orally for 7 days. Intestinal permeability was measured by the fluorescein-isothiocyanate-dextran (FITC-dextran) method. The gene expression of TJ proteins in the intestine was determined by real time-PCR. Results: FITC-dextran levels in serum were reduced by half in antibiotic-treated mice, indicating a reduction of intestinal permeability. Antibiotics increased the expression of zonula occludens 1 (ZO-1), junctional adhesion molecule A (JAM-A, and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon. Conclusion: The combination of neomycin and bacitracin reduce intestinal permeability and increase the gene expression of ZO-1, junctional adhesion molecule A (JAM-A), and occludin in the ileum and ZO-1, claudin-3, and claudin-4 in the colon (AU)


Assuntos
Animais , Feminino , Masculino , Camundongos , Permeabilidade , Neomicina/uso terapêutico , Bacitracina/uso terapêutico , Microbiota , Colo , Colo/metabolismo , Proteínas de Transporte/metabolismo , Ocludina/uso terapêutico , Claudina-3/uso terapêutico , Claudina-4/uso terapêutico , RNA Mensageiro/uso terapêutico
10.
J. physiol. biochem ; 71(2): 217-226, jun. 2015.
Artigo em Inglês | IBECS | ID: ibc-140530

RESUMO

To investigate whether uric acid could regulate urate transporter 1 (URAT1) protein and activity level, we established uric acid nephropathy (UAN) rat model and detected their serum uric acid and URAT1 level with or without the treatment of allopurinol. Results here showed that allopurinol could reduce serum uric acid level in UAN rat model. We further found that in UAN rats, the total and surface URAT1 expression level were both increased while this increase could be blocked by allopurinol treatment. By treating URAT1 stable expressed HEK cell with monosodium urate (MSU) crystals, we found that URAT1 level showed an increase in both total and cell surface level, and it would colocalize more with Rab11 instead of Rab7. Consistently, we also found that the total URAT1 protein level will show an increase in the presence of lysosome inhibitors but not ubiquitin-proteasome inhibitors. Furthermore, we also found that MSU crystal could drive Numb, a clathrin-coated adaptor protein which performs a key function in cell division, out of cell surface and disassociated it from URAT1. Finally, we found that Numb short hairpin RNA (shRNA)-transfected showed a phenocopy as MSU treatment, while Numb-2A mutation over-expression could resist crystal-induced phenotypes. These findings indicated that uric acid crystal could increase URAT1 membrane distribution through inhibiting Numb-induced URAT1 lysosome degradation (AU)


No disponible


Assuntos
Animais , Ratos , Ácido Úrico/efeitos adversos , Nefropatias/induzido quimicamente , Lisossomos/fisiologia , Urato Oxidase/fisiologia , Cristalização , Proteínas de Transporte , Alopurinol/farmacocinética , Células HEK293
11.
Med. intensiva (Madr., Ed. impr.) ; 39(4): 207-212, mayo 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-138285

RESUMO

Objetivos 1) Valorar la utilidad pronóstica de la determinación inicial y seriada de la proteína fijadora de lipopolisacáridos (LBP) y de la procalcitonina (PCT) y 2) evaluar si su adicción a los scores de gravedad mejoraría su valor pronóstico. Diseño Estudio prospectivo observacional. Ámbito Unidad de Cuidados Intensivos de un hospital general universitario. Pacientes Se incluyó a 100 pacientes ingresados por sepsis grave/shock séptico. Variables de interés Datos demográficos, APACHE II y SOFA, concentración de PCT y LBP inicial y a las 48 h y mortalidad hospitalaria. Resultados Los scores APACHE II al ingreso y SOFA a las 48 h presentaron el mayor rendimiento como predictores de mortalidad hospitalaria (AUC ROC: 0,75 para ambos). La concentración inicial de PCT y LBP y el aclaramiento de LBP fueron similares en pacientes supervivientes y fallecidos. Solo el aclaramiento de PCT fue superior en supervivientes respecto a los fallecidos (AUC ROC: 0,66). La combinación de los scores de gravedad con el aclaramiento de PCT no mejoró su valor pronóstico. Conclusiones La concentración inicial de LBP y de PCT y el aclaramiento de LBP no presentaron valor pronóstico en pacientes con sepsis grave/shock séptico. Solo el aclaramiento de PCT se comportó como predictor de mortalidad hospitalaria. El rendimiento de los scores APACHE II al ingreso y SOFA a las 48 h fue superior al de los biomarcadores analizados y la adición del aclaramiento de PCT no aumentó su valor pronóstico (AU)


Aims 1) To assess the prognostic value of levels on admission and serial measurements of lipopolysaccharide binding protein (LBP) and procalcitonin (PCT) in relation to in-hospital mortality; and 2) to determine whether the addition of these parameters to severity scores (APACHE II and SOFA) is able to improve prognostic accuracy. Design A single-center, prospective observational study was carried out. Setting Intensive Care unit of a university hospital. Patients One hundred severe sepsis and septic shock patients were included. Data collected Demographic data, APACHE II and SOFA scores, PCT and LBP levels on admission and after 48hours, and in-hospital mortality. Results The best area under the curve for predicting in-hospital mortality corresponded to APACHE II on admission and SOFA after 48h (AUC ROC: 0.75 for both). PCT and LBP levels on admission and LBP clearance were not statistically different between in-hospital survivors and non-survivors. Only PCT clearance was higher among in-hospital survivors than in non-survivors (AUC ROC: 0.66). The combination of severity scores and PCT clearance did not result in superior areas under the curve. Conclusions LBP and PCT levels on admission and LBP clearance showed no prognostic value in severe sepsis and septic shock patients. Only PCT clearance was predictive of in-hospital mortality. The prognostic accuracy was significantly better for APACHE on admission and SOFA after 48h than for any of the analyzed biomarkers, and the addition of PCT clearance did not improve their prognostic value (AU)


Assuntos
Humanos , Lipopolissacarídeos/análise , Proteínas de Transporte/análise , Receptores da Calcitonina/metabolismo , Mortalidade Hospitalar , Biomarcadores/análise , Estudos Prospectivos
12.
Acta pediatr. esp ; 72(9): 182-186, oct. 2014. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-129392

RESUMO

Introducción: El objetivo del presente estudio es analizar el comportamiento de la calprotectina fecal en los pacientes pediátricos con enfermedad celiaca, comparando sus niveles mientras recibían dieta con y sin gluten. También se han incluido en la comparación pacientes sanos y con diversas patologías digestivas no inflamatorias. Material y métodos: Se han recogido muestras de heces de pacientes celiacos con diagnóstico de novo (con gluten) y pacientes en seguimiento (sin gluten). Se incluyeron en el grupo control niños sanos sin patología digestiva y otros con diversos trastornos digestivos no diagnosticados de enfermedad inflamatoria intestinal. Resultados: La calprotectina fecal fue significativamente más alta en los pacientes celiacos que recibieron una dieta con gluten (119,2 ± 122,6 µg/g) que en los que recibieron una dieta sin gluten (21,5 ± 24,7 µg/g). Estos últimos presentaron valores similares al grupo control sano. Conclusiones: La calprotectina fecal está elevada en los pacientes celiacos con ingesta de gluten respecto a los celiacos con dieta sin gluten y los pacientes sanos. Este marcador podría usarse para la detección precoz de la ingesta de gluten (AU)


Introduction: The objective of the present research is to study the behavior of the faecal calprotectin in the pediatric coeliac disease, comparing its levels while receiving a diet with and without gluten. For the comparison, there were also included healthy children, and patients with diverse non-inflammatory digestive pathologies. Materials and methods: There have been collected stool samples from de novo coeliac patients (with gluten) and from follow-up coeliac patients (without gluten). As control groups, there were included healthy children without any digestive pathology and others with diverse digestive non-diagnosed disorders from the inflammatory bowel disease. Results: The faecal calprotectin was significantly higher in the coeliac patients with gluten (119.2 ± 122.6 µg/g) than in the patients with the gluten-free diet (21.5 ± 24.7 µg/g). The later showed similar values to those in the healthy control group. Conclusions: The faecal calprotectin is higher in the coeliac patients with gluten ingestion than in the coeliac patients with the gluten-free diet and in the healthy group. This could be used as a marker for early detection of gluten ingestion (AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Proteínas de Transporte/análise , Proteínas de Ligação ao Cálcio/análise , Doença Celíaca/fisiopatologia , Inflamação/fisiopatologia , Fezes/química , Mediadores da Inflamação/análise , Biomarcadores/análise
15.
Med. clín (Ed. impr.) ; 136(supl.1): 10-15, ene. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-141328

RESUMO

CINCA/NOMID es un síndrome conocido clínicamente desde 1981, mejor identificado en 1987 y cuya causa principal, si bien parece no ser única, fue descubierta en el año 2001 al encontrar mutaciones en el gen CIAS1 que modificaban la estructura de la proteína criopirina. A los síntomas principales que dieron lugar al nombre del síndrome —afectación neurológica, cutánea y articular— se han añadido otros síntomas menores pero muy constantes en los pacientes identificados: alteraciones pre y perinatales, rasgos morfológicos singulares y brotes febriles que se acompañan de alteraciones analíticas que ponen de manifiesto la existencia de un estado inflamatorio persistente. Los estudios radiológicos han podido identificar el origen fisario de las malformaciones osteoarticulares. CINCA/NOMID debe ser diferenciado de otros cuadros clínicos de comienzo similar en la época neonatal y primera infancia: artritis idiopática juvenil sistémica, fiebre periódica asociada al déficit de mevalonato cinasa, deficiencia humana del antagonista del receptor de IL-1 (DIRA) y síndrome de Muckle-Wells (AU)


CINCA/NOMID syndrome was first reported in 1981, identified as a new disease in 1987 and the main cause discovered in 2001, when mutations in the CIAS1 gene modifying the structure of the protein cryopirin were found in those patients (although other factors seem to play a role). Together with the major symptoms that characterized the syndrome, neurological, cutaneous and articular manifestations, others have been added which seem to be quite constant among CINCA/NOMID diagnosed patients: pre and perinatal symptoms, morfological changes, outbreaks of fever and biological abnormalities which reveal a persistent inflammatory background. The radiological studies have been able to identify the physis as the origin of the osteoarticular malformations seen in this syndrome. Diferential diagnosis includes diseases with similar onset at the neonatal period or infancy: systemic onset juvenile idiopathic athritis, periodic fever associated with mevalonate kinase deficiency, deficiency of IL-1 receptor antagonist (DIRA) and Muckle-Wells syndrome (AU)


Assuntos
Feminino , Humanos , Gravidez , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/epidemiologia , Síndromes Periódicas Associadas à Criopirina/genética , Síndromes Periódicas Associadas à Criopirina/fisiopatologia , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/diagnóstico , Idade de Início , Artralgia/etiologia , Artralgia , Diagnóstico Diferencial , Suscetibilidade a Doenças , Doenças Fetais/etiologia , Transtornos do Crescimento/etiologia , Doenças do Sistema Nervoso/etiologia , Trabalho de Parto Prematuro/etiologia , Fenótipo , Urticária/etiologia
16.
Med. clín (Ed. impr.) ; 136(supl.1): 16-21, ene. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-141329

RESUMO

El síndrome autoinflamatorio familiar inducido por frío (FCAS) y el síndrome de Muckle-Wells forman parte del grupo de criopirinopatías o síndromes asociados a criopirina (CAPS) que presentan en común la presencia de mutaciones en el gen CIAS1. Los pacientes con diagnóstico de FCAS, aunque constituyen las formas clínicas más leves de este grupo, debutan en los primeros meses de vida y los síntomas se presentan tras la inducción por frío. El diagnóstico diferencial se plantea con los síndromes de urticarias adquiridas (ACU) y los síndromes familiares por frío atípicos (FACUS). Respecto al síndrome de Muckle-Wells (MWS) presenta, además de la fiebre y el exantema urticarial como síntomas recurrentes, la sordera neurosensorial progresiva que afectará al 60% de los pacientes, que junto con la amiloidosis secundaria ensombrecerá el pronóstico de este síndrome (AU)


Familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS) belong to the cryopyrin-associated periodic syndromes (CAPS) with CIAS1 gene mutations as a common molecular basis. Patients with FCAS have the least severe clinical phenotype but are characterized by the development of symptoms induced by a generalized exposure to cold appearing during the first months of childhood. It is important to make differential diagnosis between FCAS and acquired cold urticaria (ACU) and familial atypical cold urticaria (FACU). Muckle-Wells syndrome is characterized by recurrent fever and urticarial rash, progressive sensorineural deafness and the development of secondary amyloidosis, but it is not considered the most severe disease of this group. Sensorineural deafness and amyloidosis are the two major complications of MWS and determine poor prognosis of the disease (AU)


Assuntos
Humanos , Temperatura Baixa/efeitos adversos , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Síndromes Periódicas Associadas à Criopirina/etiologia , Síndromes Periódicas Associadas à Criopirina/genética , Doenças Hereditárias Autoinflamatórias/classificação , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/etiologia , Doenças Hereditárias Autoinflamatórias/genética , Idade de Início , Amiloidose/etiologia , Artralgia/etiologia , Proteínas de Transporte/genética , Diagnóstico Diferencial , Perda Auditiva Neurossensorial/etiologia , Fenótipo , Prognóstico , Urticária/diagnóstico , Urticária/etiologia
17.
Med. clín (Ed. impr.) ; 136(supl.1): 22-28, ene. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-141330

RESUMO

El gen NLRP3 (antiguamente denominado CIAS1) codifica para la proteína criopirina (o Nalp3), perteneciente a la familia de receptores de tipo Nod (NLR) del sistema inmune innato. La criopirina forma parte de un complejo citosólico multiproteico denominado Nalp3-inflamasoma, que participa decisivamente en la respuesta inmune innata e inflamatoria mediante la detección de señales de peligro, exógenas y endógenas, y ciertas partículas inorgánicas (asbesto, sílice). La presencia de mutaciones en el gen NLRP3 que generan una criopirina hiperfuncionante es la base molecular común de los síndromes periódicos asociados a criopirina (CAPS), que engloban tres entidades clínicas de gravedad clínica creciente (síndrome autoinflamatorio familiar inducido por frío, síndrome de Muckle-Wells y síndrome CINCA-NOMID). Esta criopirina hiperfuncionante provoca la producción aumentada y no regulada de ciertas citocinas inflamatorias (IL-1β, IL-18, IL-33), y la administración in vivo de agentes bloqueadores de IL-1 provoca una excelente respuesta terapéutica en los pacientes afectados de CAPS (AU)


NLRP3 gene (formerly known as CIAS1) encodes for cryopyrin (Nalp3) protein, which belongs to the Nod-like family of innate immune receptors. Cryopyrin recruits different adaptor and effectors proteins into a cytosolic macromolecular complex termed Nalp3-inflammasome, which senses both several pathogen-associated and damage-associated molecular patterns as well as inorganic particles (asbestos, silica), and triggers innate immune and inflammatory responses. Gain-of-function NLRP3 mutations are the common molecular basis of cryopyrin-associated periodic syndromes (CAPS), which encompasses three clinical entities along a spectrum of disease severity (familial cold autoinflammatory syndrome, Muckle-Wells syndrome and CINCA-NOMID syndrome). This hypermorphic cryopyrin provokes an increased, unregulated secretion of different inflammatory cytokines (IL-1β, IL-18, IL-33) in patients with CAPS, and in vivo administration of IL-1 blocking agents results in excellent therapeutic responses in these patients (AU)


Assuntos
Humanos , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Síndromes Periódicas Associadas à Criopirina/genética , Síndromes Periódicas Associadas à Criopirina/fisiopatologia , Inflamassomos/fisiologia , Cromossomos Humanos Par 1/genética , Citocinas , Heterogeneidade Genética , Imunidade Inata , Inflamação , Interleucina-1/antagonistas & inibidores , Mutação , Linhagem , Estrutura Terciária de Proteína
18.
Med. clín (Ed. impr.) ; 136(supl.1): 34-37, ene. 2011. tab
Artigo em Espanhol | IBECS | ID: ibc-141332

RESUMO

El canakinumab es un anticuerpo monoclonal totalmente humano frente a la IL-1¦Â que ha mostrado su eficacia en el control de los síntomas de enfermos afectados de CAPS y otros procesos autoinflamatorios. Su efecto es r¨¢pido y mantenido. En los ensayos clínicos realizados hasta la fecha, los efectos adversos notificados con m¨¢s frecuencia con el uso del fármaco han sido procesos infecciosos de distinta naturaleza, cefaleas y vértigos (AU)


Canakinumab is a fully human monoclonal antibody targeted at IL-1¦Â which has shown to be effective in the control the symptoms of patients affected by CAPS and other autoinflammatory diseases. Its effect is rapid and sustained. In clinical trials conducted up until now, the most common adverse effects reported with the use of this drug have been different types of infections, migraines and vertigo (AU)


Assuntos
Humanos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Infecções/etiologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/biossíntese , Interleucina-1beta/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/fisiologia , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Suscetibilidade a Doenças , Cefaleia/induzido quimicamente , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Regulação para Cima , Vertigem/induzido quimicamente
19.
J. physiol. biochem ; 66(2): 137-142, jun. 2010. tab
Artigo em Inglês | IBECS | ID: ibc-122837

RESUMO

No disponible


Previous studies with different results have suggested that total and bioavailable testosterone levels are modified by physical exercise. Such changes may be related to modifications in cortisol levels and could be reflected in some urine androgens. To determine how weight lifting training may affect serum and urinary androgens, we measured total serum testosterone (T), cortisol, sex hormonebinding globulin (SHBG) and urinary testosterone, epitestosterone, androsterone, and etiocholanolone, in a group of 19 elite weight lifters after 20 weeks of training. SHBG increased (from 27.5 ± 9.5 to 34.7 ± 8.1 nM, p < 0.05) whereas T/SHBG decreased significantly (from 1.10 ± 0.4 to 0.85 ± 0.3, p < 0.05). Serum total testosterone and cortisol did not change significantly. In urine, androsterone and etiocholanolone decreased significantly, whereas testosterone and epitestosterone remained unchanged. Changes in T/SHBG were related positively with changes in urinary androgens (r = 0.680, p < 0.01), and changes in SHBG were negatively related with changes in urinary androgens (r = −0.578, p < 0.01). These results suggest that intense physical activity may have an influence on the elimination of androgenic hormones due mainly to changes in their transporting protein SHBG (AU)


Assuntos
Humanos , Androgênios/urina , Globulina de Ligação a Hormônio Sexual/fisiologia , Atividade Motora/fisiologia , Testosterona/sangue , Epitestosterona/sangue , Androsterona/sangue , Etiocolanolona/sangue , Proteínas de Transporte , Esportes/fisiologia , Levantamento de Peso/fisiologia
20.
An. sist. sanit. Navar ; 32(3): 413-421, sept.-dic. 2009. ilus
Artigo em Espanhol | IBECS | ID: ibc-81677

RESUMO

La biología molecular del cáncer ha permitido identificarnuevas dianas para atacar las células tumorales.Recientemente se ha propuesto la vía de señalizaciónde la insulina y el factor de crecimiento similar a la insulinacomo una de estas dianas. En esta revisión sedescribe su función biológica, los datos de laboratorioy estudios poblacionales que alertan de su papel enel cáncer y se describen los elementos claves de estavía de señalización: los ligandos (insulina, IGF1, IGF2),sus receptores y la cascada de señales intracelular quedesencadena su activación. Así mismo se revisan lasdistintas estrategias que se están investigando parabloquearla, algunas de las cuales ya se encuentran enestudios avanzados fase III. Los datos preliminares indicanque los fármacos diseñados para bloquear esta víapueden ser una nueva arma terapéutica para los pacientesoncológicos en un futuro próximo(AU)


The molecular biology of cancer has made it possibleto identify new targets for attacking tumourouscells. One of these recently proposed targets is the insulinand insulin-like growth factor signaling pathway.This review describes its biological function, laboratorydata, population studies that warn of its role incancer, and the key elements of this signaling pathway:the ligands (insulin, IGF1, IGF2), its receptors and thecascade of intracellular signals that trigger its activation.Also reviewed are the different strategies underinvestigation for blocking it, some of which are alreadyin phase III advanced studies. The preliminary data indicatethat the medicines designed for blocking this pathwaymight be a new therapeutic weapon for oncologypatients in the near future(AU)


Assuntos
Humanos , Células Neoplásicas Circulantes , Receptor IGF Tipo 2/uso terapêutico , Receptor IGF Tipo 1/uso terapêutico , Neoplasias/tratamento farmacológico , Proteínas de Transporte/fisiologia , Ligantes , Metformina/farmacocinética
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