AG490 promotes HIF-1α accumulation by inhibiting its hydroxylation.

AG490 is a tyrphostin originally described as a Janus Activated Kinase (JAK) 2 inhibitor. AG490 also inhibits epidermal growth factor receptor (EGFR) and guanylyl cyclases (GC). More recently, AG490 was associated with oxidative stress protection in experimental acute kidney injury models. We now show that AG490 is also a strong activator of the Hypoxia Inducible Factor (HIF)-1. Under normoxic conditions HIF-1α is degraded through hydroxylation, von Hippel Lindau protein (VHL)-mediated ubiquitin tagging and proteasomal degradation. AG490 increased HIF-1α protein, but not HIF-1α mRNA levels, dose- and time-dependently in cultured endothelial, vascular smooth muscle and kidney proximal tubular epithelial cells. AG490 increased HIF-1α protein half-life, suggesting that HIF-1α protein accumulation resulted from a decreased degradation. In this regard, AG490 prevented HIF-1α hydroxylation and increased HIF-1α protein levels in human renal carcinoma cells expressing VHL, but did not further increase HIF-1α in VHL negative cells. AG490 did not prevent the proteasomal degradation of other proteins. HIF-1α was not upregulated by dominant negative JAK2constructs, tyrphostin AG9, the EGFR inhibitors erbstatin and genistein, the GC inhibitor Ly83583 or cGMP analogues. Finally, AG490 also increased HIF-1α transcriptional activity evidenced by the increased HIF-1α-dependent VEGF expression. In conclusion, AG490 is a novel HIF-1α activator that increases HIF-1α half-life and protein levels through interference with HIF-1α hydroxylation and VHL-mediated degradation. This action may contribute to the cell and tissue protective effects of AG490.

Heterocigosis compuesta para las mutaciones intrón 9 + 1 g > T y Leu 850pro en el gen SLC12A3 en el Síndrome de Gitelman / No disponible

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Nephrotic syndrome complicating chronic visceral leishmaniasis: re-emergence in patients with AIDS.

Leishmania infection may be associated with immunecomplex-mediated glomerular injury. Contrary to immune-competent individuals, leishmaniasis in HIV patients is a chronic, relapsing disease. Despite the increasing frequency of the Leishmania/ HIV co-infection, there is a paucity of information on the effects of such co-infection in the kidney. We present a patient with AIDS and refractory, relapsing visceral leishmaniasis who developed nephrotic syndrome associated with renal involvement by Leishmania in the absence of immunecomplex glomerular deposition. For the first time, the relapsing nature of renal injury in this context is documented.

Síndrome antifosfolípido primario: dormido, no curado / No disponible

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Variabilidad en las medidas de tensión arterial realizada por estudiantes de 5. º y 6. º de medicina / Variability of arterial pressure measurements performed by advanced medical students

Introducción. No se ha definido objetivamente si los estudiantes de medicina avanzados dominan destrezas básicas, como la medida de tensión arterial. Sujetos métodos. Se determinó la variabilidad de medida de tensión arterial por estudiantes de 5.º y 6.º cursos demedicina. Resultados. Se encontraron coeficientes de variación significativamente más elevados en la tensión arterial diastólica derecha y frecuencia cardíaca, y grupos e individuos con error sistemático de medición. Conclusión. Resulta necesario un refuerzo docente en la medida de tensión arterial diastólica y su realización enlos dos brazos (AU)

Introduction. No objective data are available to know whether advanced medical students are in command of basic practical skills, i.e., arterial pressure measurement. Subjects and methods. Variability of arterial pressure measurements was examined in 5th- and 6th-year medical students. Results. Significantly higher variability coefficients were founding right arm diastolic arterial pressure and heart rate. A systematic measurement error was detected in some groups and individuals. Conclusion. A teaching effort will be necessary to improve arterial pressure measurement skills, with special emphasis in diastolic arterial pressure and bilateral measurements (AU)

Crioglobulinemia mixta en pacientes con doble infección por VCH/VIH: análisis del crioprecipitado como herramienta de decisión terapéutica / Mixed cryoglobulinemia in patients with dual HCV/HIV infection: analysis of cryoprecipitate as a therapeutic decision tool

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Insuficiencia renal por enfermedad de depósito de cadenas ligeras / Renal failure due to light chain deposition disease

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La aldosterona aumentala calcificación vascularin vitro / Aldosterone increases vascular calcification in in vitro studies

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Riñón pequeño envasculitis renal ANCA positiva: un posible marcador de evolución subaguda / Small kidney in ANCA-positive renal vasculitis: a possible marker of subacute evolution

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Vigencia de la acetazolamida en la terapéutica diurética actual: aplicaciones en el edema refractario y la hiperpotasemia relacionada al bloqueo aldosterónico / Actuality of the use of acetazolamide as a diuretic: usefulness in refractory edema and in aldosteroneantagonist- related hyperkalemia

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[Fluid therapy in surgical patients: composition and influences on the internal milieu]. / Sueros empleados en enfermos quirúrgicos: composición y efectos sobre el medio interno.

UNLABELLED: Intravenous fluids administration is the usual practice in the postoperative period. Nonetheless, consensus about the more appropriate fluid reposition recipe is still insufficient. OBJECTIVE: To study the type of intravenous reposition used in Surgical Units and its impact on the internal milieu. DESIGN: prospective study of 112 patients with scheduled surgery, receiving only intravenous fluids. METHODS: biochemical study on postoperative fluids management in uncomplicated surgery. Principal variables: 1. Water and electrolytes administrated. 2. Differences in sodium/water balances before surgery vs first day after surgery. 3. Symptoms related to hyponatremia. RESULTS: Median P[Na] before and after surgery was 139.9+/-2.9 and 137.7+/-3.7, respectively (p<0.01). Fourteen patients (12.5%) had P[Na]<135, and 12 of them had a reduction of more than 6 mmol/L; accordingly, twenty-six patients (23.2%) had an increased free-water retention (p<0.05). Relevantly, they did not receive a higher amount of free-water and the proportion of isotonic saline/free water varied from <1 to >3. As possible mechanism of free-water accumulation: the postoperative P[Na] was lower in the patients who had a negative free-water clearance >or= -1 L (136.7+/-4.1 vs 138.5+/-3.2 mmol/L, p 0.015). CONCLUSION: The present study provides new information about the intravenous fluids prescribed in postoperative patients, ie, different proportions saline/water are basically equivalent with respect to inducing symptomatic hyponatremia. The mean value of the relation saline/water is 2:1. Hypotonic fluids input is not clearly related to more intense hyponatremia; the latter appears to depend more on a reduced capacity of the kidney to generate sufficient free water output.

Sueros empleados en enfermos quirúrgicos: composición y efectos sobre el medio interno / Fluid therapy in surgical patients: composition and influences on the internal milieu

La prescripción de sueros en el postoperatorio es una práctica rutinaria, pero sobre la que no existe un consenso basado en la evidencia. Objetivo: Examinar sistemáticamente el tipo de reposición hidroelectrolítica empleado por los Servicios Quirúrgicos y sus consecuencias sobre el medio interno. Pacientes y métodos: Diseño: estudio prospectivo en 112 pacientes con cirugías programadas. Método: estudio bioquímico del manejo hidroelectrolítico en postoperatorios no complicados tratados solo con sueros intravenosos. Variables principales: 1. agua y electrolitos administrados; 2. Diferencias de equilibrio hidrosalino entre pre- y post-operatorio;3. alteraciones clínicas atribuíbles a hiponatremia. Resultados: La [Na]P media pre y postoperatoria fue 139,9± 2,9 y 137,7 ± 3,7, respectivamente (p < 0,01) Catorce pacientes(12,5%) alcanzaron [Na]P < 135 mmol/L, y 12 presentaron un descenso de [Na]P ≥ 6 mmol/L, vg, 26 sujetos(23,2%) tuvieron un incremento significativo de agua libre(p < 0,05) Estos pacientes no habían recibido mayor cantidad de agua libre que el resto, siendo la proporción sueros isotónicos/agua libre desde < 1 a > 3. Como posible mecanismo de la retención hídrica, la [Na]P postoperatoria en los pacientes con aclaramiento de agua libre negativo ≥ -1litro/24 h fue más baja (136,7 ± 4,1 vs 138,5 ± 3,2 mmol/L,p 0,015). Conclusiones: Se aporta información previamente no disponible: a) diversas proporciones de suero isotónico: agua libre resultaron equivalentes frente al desarrollo de hiponatremia sintomática; b) la relación media suero isotónico: agua libre es 2:1, y c) las soluciones de reposición más hipotónicas no aparecen relacionadas con más hiponatremias. Éstas en cambio dependen de la respuesta renal de retención de agua (AU)

Intravenous fluids administration is the usual practice in the post operative period. Nonetheless, consensus about the more appropriate fluid reposition recipe is still insufficient. Objective: To study the type of intravenous reposition used in Surgical Units and its impacton the internal milieu. Patients and methods: Design: prospective study of 112 patients with scheduled surgery, receiving only intravenous fluids. Methods: biochemical study on postoperative fluids management in uncomplicated surgery. Principal variables: 1. Water and electrolytes administrated. 2. Differences in sodium/water balances before surgery vs first day after surgery. 3. Symptoms related to hyponatremia. Results: Median P[Na] before and after surgery was 139.9 ± 2.9 and 137.7 ± 3.7, respectively (p< 0.01). Fourteen patients (12.5%) had P[Na] < 135, and 12 ofthem had a reduction of more than 6 mmol/L; accordingly, twentysix patients (23.2%) had an increased free-water retention (p <0.05). Relevantly, they did not receive a higher amount of freewater and the proportion of isotonic saline/free water varied from< 1 to > 3. As possible mechanism of free-water accumulation: the postoperative P[Na] was lower in the patients who had a negative free-water clearance ≥ -1 L (136,7 ± 4,1 vs 138,5 ± 3,2 mmol/L, p0,015). Conclusion: The present study provides new information about the intravenous fluids prescribed in postoperative patients, ie, different proportions saline/water are basically equivalent with respect to inducing symptomatic hyponatremia. The mean value of the relation saline/water is 2:1. Hypotonic fluids input is not clearly related to more intense hyponatremia; the latter appears to depend more on a reduced capacity of the kidney to generate sufficient free water output (AU)