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1.
Trials ; 20(1): 651, 2019 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31779697

RESUMEN

BACKGROUND: Pruritus in patients undergoing hemodialysis is a highly prevalent complication that affects quality of life. Several medications are currently used for the treatment of uremic pruritus, but these are not satisfactory. PG102P, which is prepared from Actinidia arguta, has an immune-modulating effect on pruritus. This trial is designed to assess the antipruritic effect of PG102P compared with placebo. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial will include 80 patients undergoing hemodialysis. The patients will be randomized in a 1:1 ratio to a treatment group (PG102P 1.5 g/day) or a control group (placebo). The treatment will last for 8 weeks, followed by a 2-week observational period. During the observational period, all of the patients will maintain the antipruritic treatment previously used. The primary endpoint will be measured as the difference in visual analog scale between the groups before and after treatment. Secondary outcomes include serum levels of total immunoglobulin E, eosinophil cationic protein, potassium, calcium, phosphorus, intact parathyroid hormone, and blood eosinophil count between weeks 0 and 8. Kidney Disease and Quality of Life and Beck's Depression Inventory questionnaires will be conducted. Safety assessments and any adverse events that occur will also be evaluated. DISCUSSION: The SNUG is a clinical study that aims to investigate the antipruritic effect of PG102P to ameliorate itching in patients undergoing hemodialysis. TRIAL REGISTRATION: Clinical Trials.gov, NCT03576235. Registered on 4 July 2018.


Asunto(s)
Actinidia , Extractos Vegetales/uso terapéutico , Prurito/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal/efectos adversos , Actinidia/química , Adulto , Anciano , Método Doble Ciego , Humanos , Persona de Mediana Edad , Extractos Vegetales/efectos adversos
2.
Perit Dial Int ; 39(1): 4-12, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30692232

RESUMEN

Patients with end-stage kidney disease (ESKD) have different options to replace the function of their failing kidneys. The "integrated care" model considers treatment pathways rather than individual renal replacement therapy (RRT) techniques. In such a paradigm, the optimal strategy to plan and enact transitions between the different modalities is very relevant, but so far, only limited data on transitions have been published. Perspectives of patients, caregivers, and health professionals on the process of transitioning are even less well documented. Available literature suggests that poor coordination causes significant morbidity and mortality.This review briefly provides the background, development, and scope of the INTErnational Group Research Assessing Transition Effects in Dialysis (INTEGRATED) initiative. We summarize the literature on the transition between different RRT modalities. Further, we present an international research plan to quantify the epidemiology and to assess the qualitative aspects of transition between different modalities.


Asunto(s)
Prestación Integrada de Atención de Salud/métodos , Fallo Renal Crónico/terapia , Transferencia de Pacientes/métodos , Terapia de Reemplazo Renal/métodos , Humanos , Proyectos de Investigación
3.
Cardiovasc Res ; 113(10): 1137-1147, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28430962

RESUMEN

AIMS: Autophagy is essential to maintain tissue homeostasis, particularly in long-lived cells such as cardiomyocytes. Whereas many studies support the importance of autophagy in the mechanisms underlying obesity-related cardiac dysfunction, the role of autophagy in cardiac lipid metabolism remains unclear. In the heart, lipotoxicity is exacerbated by cardiac lipoprotein lipase (LPL), which mediates accumulation of fatty acids to the heart through intravascular triglyceride (TG) hydrolysis. METHODS AND RESULTS: In both genetic and dietary models of obesity, we observed a substantial increase in cardiac LPL protein levels without any change in messenger ribonucleic acid (mRNA). This was accompanied by a dramatic down-regulation of autophagy in the heart, as revealed by reduced levels of unc-51 like kinase-1 (ULK1) protein. To further explore the relationship between cardiac LPL and autophagy, we generated cardiomyocyte-specific knockout mice for ulk1 (Myh6-cre/ulk1fl/fl), Lpl (Myh6-cre/Lplfl/fl), and mice with a combined deficiency (Myh6-cre/ulk1fl/flLplfl/fl). Similar to genetic and dietary models of obesity, Myh6-cre/ulk1fl/fl mice had a substantial increase in cardiac LPL levels. When these mice were fed a high-fat diet (HFD), they showed elevated cardiac TG levels and deterioration in heart function. However, with combined deletion of LPL and ULK1 in Myh6-cre/ulk1fl/flLplfl/fl mice, HFD feeding did not lead to alterations in levels of TG or diacylglycerol, or in cardiac function. To further elucidate the role of autophagy in cardiac lipid metabolism, we infused a peptide that enhanced autophagy (D-Tat-beclin1). This effectively lowered LPL levels at the coronary lumen by restoring autophagy in the genetic model of obesity. This decrease in cardiac luminal LPL was associated with a reduction in TG levels and recovery of cardiac function. CONCLUSION: These results provide clear evidence of the critical role of modulating cardiac LPL activity through autophagy-mediated proteolytic clearance as a potential novel strategy to overcome obesity-related cardiomyopathy.


Asunto(s)
Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Autofagia , Ácidos Grasos/metabolismo , Cardiopatías/prevención & control , Contracción Miocárdica , Miocitos Cardíacos/enzimología , Obesidad/complicaciones , Triglicéridos/metabolismo , Animales , Homólogo de la Proteína 1 Relacionada con la Autofagia/deficiencia , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Beclina-1/metabolismo , Células Cultivadas , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Estabilidad de Enzimas , Predisposición Genética a la Enfermedad , Cardiopatías/enzimología , Cardiopatías/patología , Cardiopatías/fisiopatología , Hidrólisis , Preparación de Corazón Aislado , Lipólisis , Lipoproteína Lipasa/genética , Lipoproteína Lipasa/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/patología , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Obesidad/enzimología , Obesidad/patología , Obesidad/fisiopatología , Fenotipo , Proteolisis , Transducción de Señal , Factores de Tiempo
4.
Yonsei Med J ; 57(5): 1159-64, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27401647

RESUMEN

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: ß=0.263, p<0.001; age: ß=0.122, p=0.010; ESA dose: ß=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.


Asunto(s)
Anemia/etiología , Fallo Renal Crónico/complicaciones , Deficiencia de Vitamina D/complicaciones , Adulto , Anciano , Anemia/sangre , Calcifediol , Estudios Transversales , Femenino , Hemoglobina A/análisis , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Análisis de Regresión , Factores de Riesgo , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre
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