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2.
Biomed Pharmacother ; 142: 112090, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34463266

RESUMEN

BACKGROUND: MicroRNAs play an important role in health and disease. TGF-ß signaling, upregulated by HIV Tat, and in chronic airway diseases and smokers upregulates miR-145-5p to suppress cystic fibrosis transmembrane conductance regulator (CFTR). CFTR suppression in chronic airway diseases like Cystic Fibrosis, COPD and smokers has been associated with suppressed MCC and recurrent lung infections and inflammation. This can explain the emergence of recurrent lung infections and inflammation in people living with HIV. METHODS: Tat-induced aberrant microRNAome was identified by miRNA expression analysis. microRNA mimics and antagomirs were used to validate the identified miRNAs involved in Tat mediated CFTR mRNA suppression. CRISPR-based editing of the miRNA target sites in CFTR 3'UTR was used to determine rescue of CFTR mRNA and function in airway epithelial cell lines and in primary human bronchial epithelial cells exposed to TGF-ß and Tat. FINDINGS: HIV Tat upregulates miR-145-5p and miR-509-3p. The two miRNAs demonstrate co-operative effects in suppressing CFTR. CRISPR-based editing of the miRNA target site preserves CFTR mRNA and function in airway epithelial cells INTERPRETATION: Given the important roles of TGF-ß signaling and the multitude of genes regulated by miRNAs, we demonstrate that CRISPR-based gene-specific microRNA antagonism approach can preserve CFTR mRNA and function in the context of HIV Tat and TGF-ß signaling without suppressing expression of other genes regulated by miR-145-5p.


Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , MicroARNs/genética , ARN Mensajero/genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Regiones no Traducidas 3'/genética , Bronquios/citología , Sistemas CRISPR-Cas/genética , Línea Celular , Células Cultivadas , Células Epiteliales/metabolismo , Edición Génica , Humanos , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba
3.
Sci Rep ; 10(1): 20797, 2020 11 27.
Artículo en Inglés | MEDLINE | ID: mdl-33247145

RESUMEN

Continuous renal replacement therapies (CRRT) affect hemodynamics and urine output. Some theories suggest a reduced renal blood flow as the cause of the decreased urine output, but the exact mechanisms remain unclear. A prospective experimental study was carried out in 32 piglets (2-3 months old) in order to compare the impact of CRRT on hemodynamics, renal perfusion, urine output and renal function in healthy animals and in those with non-oliguric acute kidney injury (AKI). CRRT was started according to our clinical protocol, with an initial blood flow of 20 ml/min, with 10 ml/min increases every minute until a goal flow of 5 ml/kg/min. Heart rate, blood pressure, central venous pressure, cardiac output, renal blood flow and urine output were registered at baseline and during the first 6 h of CRRT. Blood and urine samples were drawn at baseline and after 2 and 6 h of therapy. Blood pressure, cardiac index and urine output significantly decreased after starting CRRT in all piglets. Renal blood flow, however, steadily increased throughout the study. Cisplatin piglets had lower cardiac index, higher vascular resistance, lower renal blood flow and lower urine output than control piglets. Plasma levels of ADH and urine levels of aquaporin-2 were lower, whereas kidney injury biomarkers were higher in the cisplatin group of piglets. According to our findings, a reduced renal blood flow doesn't seem to be the cause of the decrease in urine output after starting CRRT.


Asunto(s)
Terapia de Reemplazo Renal Continuo/efectos adversos , Hemodinámica , Circulación Renal , Urodinámica , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/terapia , Animales , Biomarcadores/sangre , Biomarcadores/orina , Presión Sanguínea , Niño , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Estudios Prospectivos , Porcinos , Porcinos Enanos , Resistencia Vascular
4.
Med Intensiva (Engl Ed) ; 43(5): 281-289, 2019.
Artículo en Inglés, Español | MEDLINE | ID: mdl-29605581

RESUMEN

OBJECTIVES: To analyze the hematological complications and need for transfusions in children receiving extracorporeal life support (ECLS). DESIGN: A retrospective study was carried out. SETTING: A pediatric intensive care unit. PATIENTS: Children under 18 years of age subjected to ECLS between September 2006 and November 2015. INTERVENTIONS: None. VARIABLES OF INTEREST: Patient and ECLS characteristics, anticoagulation, hematological and coagulation parameters, transfusions and clinical course. RESULTS: A total of 100 patients (94 with heart disease) with a median age of 11 months were studied. Seventy-six patients presented bleeding. The most frequent bleeding point was the mediastinum and 39 patients required revision surgery. In the first 3days, 97% of the patients required blood transfusion (34.4ml/kg per day), 94% platelets (21.1ml/kg per day) and 90% plasma (26.6ml/kg per day). Patients who were in the postoperative period, those who were bleeding at the start of ECLS, those requiring revision surgery, those who could not suspend extracorporeal circulation, and those subjected to transthoracic cannulation required a greater volume of transfusions than the rest of the patients. Thromboembolism occurred in 14 patients and hemolysis in 33 patients. Mortality among the children who were bleeding at the start of ECLS (57.6%) was significantly higher than in the rest of the patients (37.5%) (P=.048). CONCLUSIONS: Children subjected to ECLS present high blood product needs. The main factors related to transfusions were the postoperative period, bleeding at the start of ECLS, revision surgery, transthoracic cannulation, and the impossibility of suspending extracorporeal circulation. Children with bleeding suffered greater mortality than the rest of the patients.


Asunto(s)
Oxigenación por Membrana Extracorpórea/efectos adversos , Enfermedades Hematológicas/etiología , Hemorragia/etiología , Transfusión Sanguínea/estadística & datos numéricos , Preescolar , Femenino , Enfermedades Hematológicas/terapia , Hemorragia/terapia , Humanos , Lactante , Masculino , Estudios Retrospectivos
5.
An Pediatr (Barc) ; 83(6): 404-9, 2015 Dec.
Artículo en Español | MEDLINE | ID: mdl-25683273

RESUMEN

INTRODUCTION: The objective of this study is to analyze long-term outcomes and kidney function in children requiring continuous renal replacement therapy (CRRT) after an acute kidney injury episode. PATIENTS AND METHODS: A retrospective observational study was performed using a prospective database of 128 patients who required CRRT admitted to the pediatric intensive care unit between years 2006 and 2012. The subsequent outcomes were assessed in those surviving at hospital discharge. RESULTS: Of the 128 children who required RRT in the pediatric intensive care unit, 71 survived at hospital discharge (54.4%), of whom 66 (92.9%) were followed up. Three patients had chronic renal failure prior to admission to the NICU. Of the 63 remaining patients, 6 had prolonged or relapses of renal function disturbances, but only one patient with atypical Hemolytic Uremic Syndrome developed end-stage renal failure. The rest had normal kidney function at the last check-up. CONCLUSIONS: Most of surviving children that required CRRT have a positive outcome later on, presenting low mortality rates and recovery of kidney function in the medium term.


Asunto(s)
Lesión Renal Aguda/terapia , Terapia de Reemplazo Renal , Niño , Fluidoterapia , Estudios de Seguimiento , Humanos , Unidades de Cuidados Intensivos , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento
6.
Nutr Hosp ; 28(4): 1219-26, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23889645

RESUMEN

INTRODUCTION: Is there a group of psychometric variables, which correlates with the criteria of an interdisciplinary team about the course of ED? OBJECTIVES: The aim of this study was to analyse the correlation between the clinic criteria of an interdisciplinary team with respect to the course of eating disorders (ED) and different psychometric criteria. METHODS: The course was analysed in a final sample of 30 ED outpatients during their six first months of treatment. A scale of clinical criteria of the course of ED (therapeutic team's opinion) and different questionnaires on psychological, psychopathological and eating-related variables were used. The statistical analysis comprised of a discriminant analysis in order to find the variables with a discriminant function to distinguish between a fair-bad course and a good course. RESULTS: Perceived stress, self-esteem, the variables of the SCL-90-R, depression, thought-shape fusion, anxiety, food craving and the score on body shape questionnaire were found to have discriminant function. Comparing the therapeutic team's criteria and the results of the questionnaires a 10% of patients were misclassified. DISCUSSION: The results highlight the necessary and permanent checking of the relationship among the clinical criteria regarding the course of ED (members' team opinion) and different psychological, psychopathological and eating-related variables.


Introducción: ¿Existe un grupo de variables psicométricas que correlacione con el criterio de un equipo terapéutico interdisciplinar acerca del curso de los trastornos de la conducta alimentaria? Objetivos: El propósito de este estudio fue analizar la correlación entre criterios clínicos de un equipo terapéutico interdisciplinar con respecto al curso de los trastornos de la conducta alimentaria y diferentes criterios psicométricos. Métodos: La evolución fue analizada en una muestra final de 30 pacientes ambulatorios con trastornos de la conducta alimentaria durante los seis primeros meses de tratamiento. Una escala de criterios clínicos (la opinión del equipo terapéutico) y diferentes cuestionarios sobre variables psicológicas, psicopatológicas y relacionadas con la conducta alimentaria fueron utilizadas. Se llevó a cabo un análisis discriminante a fin de encontrar variables con función discriminante para distinguir una buena evolución de otras evoluciones. Resultados: El estrés percibido, autoestima, las variables contenidas en el listado de síntomas de Derogatis, la fusión pensamiento-forma, ansiedad, food craving y la puntuación en el cuestionario de imagen corporal tienen una función discriminante. Comparando los criterios del equipo terapéutico con los resultados de los cuestionarios, un 10% de los pacientes resultaron estar mal clasificados. Discusión: Los resultados ponen de relieve la necesaria y permanente evaluación a llevar a cabo entre los criterios clínicos con respecto a la evolución de los pacientes y el resultado de la medición de diferentes variables psicométricas, tanto psicológicas como psicopatológicas y relacionadas con la conducta alimentaria.


Asunto(s)
Trastornos de Alimentación y de la Ingestión de Alimentos/psicología , Psicometría , Adaptación Psicológica , Anorexia/psicología , Imagen Corporal , Índice de Masa Corporal , Análisis Discriminante , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Grupo de Atención al Paciente , Calidad de Vida , Autoimagen , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Adulto Joven
7.
An. pediatr. (2003, Ed. impr.) ; 76(2): 77-82, feb. 2012. tab
Artículo en Español | IBECS | ID: ibc-101316

RESUMEN

Objetivo: Analizar la eficacia y seguridad de las dosis bajas de factor activador del plasminógeno (rt-PA) en el tratamiento de las trombosis venosas y/o arteriales en niños Pacientes y métodos: Estudio clínico prospectivo observacional en el que se estudiaron 18 pacientes de edades comprendidas entre 1 mes y 11 años que recibieron tratamiento fibrinolítico en perfusión intravenosa continua con dosis bajas de rt-PA. (0,01-0,06mg/kg/h). Resultados: Un 94% de los pacientes mejoraron con el tratamiento con dosis bajas de rt-PA (72% con resolución completa del trombo y 22% resolución parcial). Un paciente presentó una hemorragia grave y precisó suspender el tratamiento. La incidencia de efectos secundarios graves fue baja (5%). Conclusiones: El tratamiento con dosis bajas de rt-PA (0,01-0,05mg/kg/h) es efectivo en un elevado porcentaje de niños con trombosis aguda arterial y/o venosa y con un relativo bajo porcentaje de riesgo de sangrado(AU)


Objective: To analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children. Patients and methods: Prospective observational clinical study. 18 children between 1 months and 11 years treated with low doses (0.01-0.06mg/kg/h) of continuous intravenous thrombolytic therapy with t-PA were studied. Results: A total of 94% of patients improved with low doses t-PA (72% complete resolution of the thrombosis and 22% partial resolution). One patient suffered a severe haemorrhage secondary to t-Pa and had to stop the treatment. The incidence of severe side effects was low (5%). Conclusions: Thrombolytic therapy with low doses of t-PA (0.01-0.05mg/kg/h) is effective in a high percentage of children with acute arterial and/or venous thrombosis and produces a relatively low frequency of side effects(AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Terapia Trombolítica/instrumentación , Terapia Trombolítica/métodos , Plasminógeno , Activadores Plasminogénicos/uso terapéutico , Trombosis/diagnóstico , Trombosis/terapia , Perfusión , Terapia Trombolítica/tendencias , Terapia Trombolítica , Estudios Prospectivos
10.
An Pediatr (Barc) ; 76(2): 77-82, 2012 Feb.
Artículo en Español | MEDLINE | ID: mdl-21982548

RESUMEN

OBJECTIVE: To analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children. PATIENTS AND METHODS: Prospective observational clinical study. 18 children between 1 months and 11 years treated with low doses (0.01-0.06 mg/kg/h) of continuous intravenous thrombolytic therapy with t-PA were studied. RESULTS: A total of 94% of patients improved with low doses t-PA (72% complete resolution of the thrombosis and 22% partial resolution). One patient suffered a severe haemorrhage secondary to t-Pa and had to stop the treatment. The incidence of severe side effects was low (5%) CONCLUSIONS: Thrombolytic therapy with low doses of t-PA (0.01-0.05 mg/kg/h) is effective in a high percentage of children with acute arterial and/or venous thrombosis and produces a relatively low frequency of side effects.


Asunto(s)
Fibrinolíticos/administración & dosificación , Terapia Trombolítica , Trombosis/tratamiento farmacológico , Activador de Tejido Plasminógeno/administración & dosificación , Adolescente , Niño , Preescolar , Femenino , Fibrinolíticos/efectos adversos , Humanos , Lactante , Masculino , Estudios Prospectivos , Activador de Tejido Plasminógeno/efectos adversos
11.
Eur J Clin Nutr ; 62(3): 395-400, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17327861

RESUMEN

OBJECTIVE: To study the risk factors for gastrointestinal complications related to enteral nutrition in critically ill children. DESIGN: A prospective, observational study. SETTING: Pediatric intensive care unit. SUBJECTS: Five hundred and twenty-six critically ill children who received transpyloric enteral nutrition(TEN). METHODS: Univariate and multivariate logistic regression analysis were used to identify risk factors for gastrointestinal complications. RESULTS: Sixty six patients (11.5%) presented gastrointestinal complications, 33 (6.2%) abdominal distension and/or excessive gastric residue, 34 (6.4%) diarrhea, one gastrointestinal bleeding, three necrotizing enterocolitis and one duodenal perforation. Enteral nutrition was definitively suspended because of gastrointestinal complications in 11 (2.1%) patients. Fifty patients (9.5%) died. Gastrointestinal complications were more frequent in the patients who died. Death was related to complications of the nutrition in only one patient. The frequency of gastrointestinal complications was significantly higher in children with shock, acute renal failure, hypokalemia, hypophosphatemia and in those receiving dopamine, epinephrine and vecuronium. The stepwise multivariate logistic regression analysis showed that the most important factors associated with gastrointestinal complications were shock, epinephrine at a rate higher than 0.3 microg/kg/min and hypophosphatemia. CONCLUSIONS: The tolerance of TEN in critically ill children is good, although the incidence of gastrointestinal complications is higher in patients with shock, acute renal failure, hypokalemia, hypophosphatemia, and those receiving epinephrine, dopamine, and vecuronium.


Asunto(s)
Enfermedad Crítica/terapia , Nutrición Enteral/efectos adversos , Enfermedades Gastrointestinales/etiología , Complicaciones Posoperatorias/etiología , Lesión Renal Aguda/complicaciones , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crítica/mortalidad , Femenino , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/mortalidad , Humanos , Hipopotasemia/complicaciones , Hipofosfatemia/complicaciones , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Estudios Prospectivos , Píloro , Factores de Riesgo , Choque/complicaciones , Factores de Tiempo , Resultado del Tratamiento
13.
Acta Med Port ; 5(10): 527-32, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1492602

RESUMEN

Pulmonary embolism is a serious and difficult problem. Many approaches for the prevention of recurrent pulmonary embolism have been tried. Percutaneous placement of inferior vena cava filters is an easy, safe, available and well established procedure for the prevention of pulmonary embolism. The authors review the indications for use of IVC filters, and they review the main filters available in terms of ease of use, the physical characteristics, the technique of introduction, the efficacy and morbidity, and the potential complications associated with their use. Insertion of IVC filters by percutaneous approach was successfully performed in 6 patients with recurrent pulmonary embolism. Following the intervention procedure without complication there were no further pulmonary emboli.


Asunto(s)
Embolia Pulmonar/prevención & control , Filtros de Vena Cava , Adulto , Anciano , Diseño de Equipo , Femenino , Humanos , Métodos , Persona de Mediana Edad , Piel
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