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Introduction Urine oxalate excretion is low (normal value Oxalate is produced in the liver from glyoxylate transformation by lactate dehydrogenase type 5 (LDH5) isoenzyme and excreted in urine, with little [...], Increased urinary oxalate excretion (hyperoxaluria) promotes the formation of calcium oxalate crystals. Monogenic diseases due to hepatic enzyme deficiency result in chronic hyperoxaluria, promoting end-stage renal disease in children and young adults. Ethylene glycol poisoning also results in hyperoxaluria, promoting acute renal failure and frequently death. Stiripentol is an antiepileptic drug used to treat children affected by Dravet syndrome. It has been shown to inhibit neuronal lactate dehydrogenase 5 enzyme. As this isoenzyme is also the last step of hepatic oxalate production, we hypothesized that stiripentol would potentially reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreased the synthesis of oxalate by hepatocytes in a dose-dependent manner. In vivo, oral administration of stiripentol significantly reduced urine oxalate excretion in rats. Stiripentol protected the kidneys against calcium oxalate crystal deposits in acute ethylene glycol intoxication and chronic calcium oxalate nephropathy models. In both models, stiripentol significantly improved renal function. Patients affected by Dravet syndrome and treated with stiripentol had a lower urine oxalate excretion than control patients. A young girl affected by severe type I hyperoxaluria received stiripentol for several weeks, and urine oxalate excretion decreased by two-thirds. Stiripentol is a promising potential therapy against genetic hyperoxaluria and ethylene glycol poisoning.

In the United States, recreational water is a relatively uncommon source of Shiga toxin-producing Escherichia coli (STEC) O157 outbreaks (1). We describe an outbreak of STEC O157 infections among children [...]

Introduction Worldwide, over two million children are infected by human immunodeficiency virus type l (HIV-1). (1) Ninety per cent of them live in Africa, and only 38% of those who [...], Objective To assess 12-month survival, pharmacokinetics, immunologic and virologic efficacy, tolerance, compliance and drug resistance in HIV-infected children in Bobo-Dioulasso, Burkina Faso, receiving once-daily highly-active antiretroviral therapy as a combination of didanosine (DDI), lamivudine (3TC) and efavirenz (EFV). Methods In the ANRS 12103 open phase II trial, HIV-infected children were examined at inclusion and monthly thereafter. CD4+ T-lymphocyte (CD4) count, plasma concentration of ribonucleic acid (RNA) of human immunodeficiency virus type 1 (HIM-1) and haematologic and biochemical parameters were measured at baseline and every trimester. HIV-1 resistance testing was performed in case of viral escape. Drug plasma concentrations were determined with high-performance liquid chromatography. Findings From February 2006 to November 2007, 51 children (39% girls) with a mean age of 6.8 years were enrolled and treated for 12 months. At baseline, Z scores for mean weight-for-age and mean height-for-age were -2.01 and -2.12, respectively. Mean CD4% was 9.0. Median plasma HIV-1 RNA viral load was 5.51 [log.sub.10] copies per millilitre (cp/ml). Two children (3.9%) died and another 11 (22%) suffered 13 severe clinical events. At month 12, mean WAZ had improved by 0.63 (P< 0.001) and mean HAZ by 0.57 (P< 0.001). Mean CD4% had risen to 24 (P< 0.001). Viral load was below 300 RNA cp/ml in 81% of the children; HIV resistance mutations were detected in 11 (21.6%). Conclusion The once-a-day combination of DDI + 3TC + EFV is an alternative first-line treatment for HIV-1-infected children. Dose adjustment should further improve efficacy. Objectif Evaluer sur 12 mois la survie, la pharmacocinetique, l'efficacite immunologique et virologique, la tolerance, l'observance et la resistance au medicament chez des enfants infectes par le VlH a Bobo-Dioulasso, Burkina Faso, et qui recoivent une fois par jour une therapie antiretrovirale hautement active par une association de didanosine (DDI), de lamivudine (3TC) et d'efavirenz (EFV). Methodes Dans l'essai ouvert ANRS 12103 phase II, des enfants infectes par le VlH ont ete examines au moment de l'inclusion et ensuite chaque mois. Le taux de lymphocytes T CD4 (CD4), la concentration plasmatique d'acide ribonucleique (ARN) du virus de l'immunodeficience humaine type 1 (VlH-1), ainsi que des parametres hematologiques et biochimiques ont ete mesures au debut de l'etude et chaque trimesb'e. Le test de resistance au VIH-1 a ete effectue dans les cas d'evasion virale. Les concentrations plasmatiques de medicament ont ete determinees par chromatographie liquide a haute performance. Resultats De fevrier 2006 a novembre 2007, 51 enfants (39% de filles), avec une moyenne d'age de 6,8 ans, ont ete selectionnes et traites pendant 12 mois. Au debut de l'etude, les ecarts reduits pour le poids moyen par age et la taille moyenne par age etaient respectivement de -2,01 et -2,12. Le CD4 moyen etait 9,0%. La charge virale plasmatique mediane de I'ANR VIH-1 etait de 5,51 legue copies par millilitre (cp/ ml). Deux enfants (3,9%) sont decedes et 11 autres (22%) ont souffert 13 evenements cliniques severes. Au 12e mois, le WAZ moyen s'etait ameliore de 0,63 (P Conclusion L'association DDI + 3TC + EFV en une prise quotidienne est un traitement alternatif de premiere intention pour les enfants infectes au VIH-1. L'adaptation de la dose devrait encore ameliorer l'efficacite. Objetivo Evaluar a 12 meses la supervivencia, la farmacocinetica, la eficacia inmunologica y virologica, la tolerancia, el cumplimiento terapeutico y la resistencia a los medicamentos en ninos infectados con el VIH en Bobo-Dioulasso (Burkina Faso), que reciben una vez al dia un tratamiento antirretrovirico muy activo, constituido por la asociacion de didanosina (DDI), lamivudina (3TC) y efavirenz (EFV). Metodos En el ensayo clinico ANRS 12103, abierto y de fase II, se examino a los ninos infectados con el VIH en el momento de la inclusion y, a continuacion, mensualmente. Se midieron el recuento de linfocitos T [CD4.sup.+] (CD4), la concentracion plasmatica de acido ribonucleico (ARN) del virus de la inmunodeficiencia humana de tipo 1 (VlH-1) y los parametros hematologicos y bioquimicos, al inicio y cada trimestre. Las pruebas de resistencia al VIH-1 se realizaron en el caso de escape virico. Las concentraciones plasmaticas del farmaco se determinaron con cromatografia en fase liquida de alta resolucion. Resultados Desde febrero del 2006 a noviembre del 2007, 51 ninos (39% ninas) con una edad media de 6,8 anos fueron registrados y tratados durante 12 meses. Al inicio del estudio, las puntuaciones Z del peso medio por edad y la altura media por edad fueron -2,01 y -2,12 respectivamente. El % medio de CD4 fue 9,0. La carga virica media de RNA del HIV-1 en plasma fue de 5,51 [log.sub.10] copias por mililitro (cp/ml). Dos ninos (3,9%) murieron y otros 11 (22%) sufrieron 13 acontecimientos clinicos graves. En el mes 12, el WAZ medio (peso por edad segun la puntuacion Z) habia mejorado en un 0,63 (p < 0,001) y el HAZ medio (altura por edad segun la puntuacion Z) en 0,57 (p < 0,001). El % medio de CD4 habia subido a 24 (p < 0,001). La carga virica estaba por debajo de 300 ARN cp/ml en el 81% de los ninos; se detectaron mutaciones de resistencia al VlH en 11 (21,6%). Conclusion La asociacion de DDI + 3TC + EFV una vez al dia es un tratamiento alternativo de primera linea para los ninos infectados con el VIH-1. Un ajuste de la dosis deberia mejorar todavia mas la eficacia.

Introduction Concomitant with the global obesity epidemic, there are a number of reports of obesity-related glomerulopathy, a secondary form of focal and segmental glomerulosclerosis characterized by proteinuria and progressive renal [...], Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears. Keywords Kidney disease * Renal function impairment. Obesity * Insulin resistance * Children * Adolescents * Nitric oxide * Oxidative stress

Introduction While congenital obstructive nephropathy constitutes the single most important identifiable cause of renal impairment in infants and children, the natural history of this disorder remains poorly understood, and indications [...], Congenital obstructive nephropathy accounts for the greatest fraction of chronic kidney disease in children. Genetic and nongenetic factors responsible for the lesions are largely unidentified, and attention has been focused on minimizing obstructive renal injury and optimizing long-term outcomes. The cellular and molecular events responsible for obstructive injury to the developing kidney have been elucidated from animal models. These have revealed nephron loss through cellular phenotypic transition and cell death, leading to the formation of atubular glomeruli and tubular atrophy. Altered renal expression of growth factors and cytokines, including angiotensin, transforming growth factor-β, and adhesion molecules, modulate cell death by apoptosis or phenotypic transition of glomerular, tubular, and vascular cells. Mediators of cellular injury include hypoxia, ischemia, and reactive oxygen species, while fibroblasts undergo myofibroblast transformation with increased deposition of extracellular matrix. Progression of the lesions involves interstitial inflammation and interstitial fibrosis, both of which impair growth of the obstructed kidney and result in compensatory growth of the contralateral kidney. The long-term outcome depends on timing and severity of the obstruction and its relief, minimizing ongoing injury, and enhancing remodeling. Advances will depend on new biomarkers to evaluate the severity of obstruction, to determine therapy, and to follow the evolution of lesions. Keywords Apoptosis * Biomarkers * Fibrosis * Growth factors * Inflammation * Recovery