Assessment of in-utero venlafaxine induced, ROS-mediated, apoptotic neurodegeneration in fetal neocortex and neurobehavioral sequelae in rat offspring.

Venlafaxine (VEN), a serotonin and noradrenaline reuptake inhibitor is being used as a drug of choice for treating clinical depression even during pregnancy. It is an important therapeutic option in the treatment of perinatal depression, but the effects of VEN on fetus and the newborn are uncertain. Therefore, present study was undertaken to investigate the safety of in-utero exposure to VEN in terms of developmental neurotoxicity and neurodegenerative potential by using prenatal rat model. The selected doses of VEN (25, 40 and 50mg/kg) were administered to pregnant rats from GD 5 to 19 through oral gavage. The fetal brains were dissected and processed for histopathological measurements of neocortical thickness that showed significant reduction. Considering vulnerability of immature brain to free radical injury, VEN exposed neocortices were tested for reactive oxygen species (ROS) levels which were significantly increased. As ROS play important role in the initiation of apoptotic mechanisms, we explored for in situ detection of apoptosis by confocal microscopy that showed enhanced apoptosis including chromatin condensation which was further reconfirmed by electron microscopy. Substantially increased levels of pro-apoptotic protein Bax and decreased levels of anti-apoptotic protein Bcl2 as shown by western blotting also supported the increased neuro-apoptotic degeneration. For further correlation of these findings, prenatally VEN exposed young-adult rat offspring were assessed for open field exploratory behavior that showed increased anxiety-like and stereotypic responses indicating disturbed neurobehavioral pattern. The study concludes that prenatal VEN exposure may primarily enhance ROS generation that plays a key role in regulating release of proapoptotic factors from mitochondria and thereby enhancing apoptotic neurodegeneration that affect proliferation, migration and differentiation of cells, resulting in neuronal deficits manifested as long term neurobehavioral impairments.

¿Debe realizarse una cistografía a todos los lactantes con dilatación leve y moderada de las vías urinarias? Las pruebas de función renal pueden ayudar a responder a esta pregunta / Should a cystography be performed on all breastfeeding infants with mild to moderate dilatation of the urinary tract? Renal function tests can help to answer this question

Introducción: La ectasia piélica puede definirse como la dilatación leve–moderada de las vías urinarias diagnosticada mediante ecografía (0,5–2 cm de diámetro transversal en la primera ecografía realizada después de nacer). Existe una cierta divergencia sobre si la cistografía se debe indicar de forma universal. El objetivo del estudio fue conocer si las pruebas de función renal son útiles para decidir, en los casos de dilatación leve y moderada de las vías urinarias, aquellos en los que no se debe solicitar la cistografía inicialmente. Pacientes y métodos: Se estudiaron 79 niños (57 niños, 22 niñas) con ectasia piélica (73, diagnosticadas intraútero y seis después de nacer). A todos se les realizaron, al menos, una cistografía y una prueba de concentración con estímulo de desmopresina antes del año de edad. Resultados: En relación con los niños sin reflujo vesicoureteral (RVU) (n = 68), los niños con RVU (n = 11; dos de grado I, tres de grado II, cinco de grado III, dos de grado IV) mostraron una osmolalidad urinaria máxima significativamente inferior (p = 0,006) y un cociente microalbúmina/creatinina (p <0,001) y un cociente NAG/creatinina (p = 0,003) significativamente superiores. El valor predictivo negativo de las dos primeras pruebas fue del 93%. La sensibilidad de la osmolalidad urinaria máxima para detectar RVU fue del 72,7% (especificidad 63,2%). La sensibilidad del cociente microalbúmina/creatinina para detectar RVU fue del 62,5% (especificidad 75%). El cociente de probabilidad (CP) positivo para el (..)(AU)

Introduction: Pyelectasis can be defined as mild to moderate dilatation of the urinary tract and is diagnosed by means of an ultrasound scan (0.5–2cm transverse diameter in the initial ultrasound performed after birth). There is some disagreement about whether cystography should be indicated as standard practice. The aim of this study was to establish if renal function tests are useful in determining which cases of mild to moderate dilatation of the urinary tract do not require an initial cystography. Patients and Methods: The study was conducted on 79 infants (57 males, 22 females) with pyelectasis. Seventy–three were diagnosed in utero and 6 after birth. All infants underwent at least one cystography and one desmopressin urine concentration test before one year of age. Results: Compared to infants without vesicoureteral reflux (VUR) (n=68), infants with VUR (n=11; two with Grade I, three with Grade II, five with Grade III, two with Grade IV) showed a significantly lower (P=.006) maximum urine osmolality and a significantly higher microalbumin/creatinine ratio (P<.001) and NAG/creatinine ratio (P=.003). The negative predictive value of the first two tests was 93%. Sensitivity of the maximum urine osmolality to detect VUR was 72.7% (specificity 63.2%). Sensitivity of the microalbumin/creatinine ratio to detect VUR was 62.5% (specificity 75%). The positive probability ratio (PR) was 1.29 for the NAG/creatinine ratio, 2.03 for the maximum urine osmolality and 2.5 for the microalbumin/creatinine ratio. The negative PR was 0.95 for the NAG/creatinine ratio, 0.43 for the maximum urine osmolality and 0.5 for the microalbumin/creatinine ratio. Conclusions: Pyelectasis is a benign condition. Only 2 patients required pharmacological intervention (prophylactic treatment for VUR Grade IV patients). Cystography should not be indicated initially, at least, in cases of microalbuminuria and/or normal urine concentrations (..) (AU)