ABSTRACT
A correlation between elevation of pro-inflammatory cytokines and white matter injury or abnormal neurological outcome has been established in the preterm infant. In the full-term neonate, few studies exist linking elevation of cytokines with encephalopathy and poor neurodevelopmental outcome. The aim of this study was to examine the relation of plasma and cerebrospinal fluid [CSF] interleukin-1 beta [IL-1beta] and tumor necrosis factor-alpha [TNF-alpha] to the severity of hypoxic-ischemic encephalopathy [HIE] and to the neurological outcome in full-term newborns with HIE. Thirty full-term neonates with HIE were included in the study. HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF were obtained within the first 24 hours of life for determination of IL-1beta and TNF-alpha by ELISA. Five neonates died soon after the hypoxic insult. Neurological examination and Denver Developmental Screening Test [DDST] were performed at 12 months in the survivors. The results showed that, at the age of 12 months, neurological examination and DDST showed that 13 infants were normal; 12 had abnormal neurological findings and/or an abnormal DDST result. Thirteen normal infants were classified as group1 and 17 infants [12 with abnormal neurological findings and/or an abnormal DDST and five who died] as group 2. CSF IL-1beta and TNF-alpha levels in-group 2 were significantly higher than those in-group1 [P = 0.0005 for IL-1beta, and P = 0.003 for TNF-alpha]. Plasma IL-1beta and TNF-alpha levels were not significantly different between the two groups [P = 0.098 for IL-1 beta, and P= 0.275 for TNF-alpha. CSF IL-1 beta but not TNF-alpha levels, in-group 2 were even higher than those in-group1, although non-survivors were excluded from group 2 [P = 0.001 for IL-1beta, and P = 0.257 for TNF-alpha]. When the patients were evaluated according to the stages of Sarnat, the differences in the three groups were significant [P = 0.002 for IL-1beta, and P = 0.03 for TNF-alpha]. Patients whose CSF samples were taken within 6 hours of the hypoxic insult had higher IL-1 beta and TNF-alpha levels than the patients whose samples were taken after 6 hours [P = 0.0001 for IL-1 beta and P = 0.015 for TNF-alpha
Conclusion: IL-1 beta and TNF-alpha probably contribute to the damage sustained by the central nervous system after hypoxic insult, and this support a recommendation for future studies with brain blockers of the actions of these cytokines for neuroprotective strategies
ABSTRACT
Vascular endothelial growth factor [VEGF] is a selective endothelial mitogen and vascular permeability factor that is mainly produced by activated monocytes/ macrophages and T-cells. It enhances endothelial cell proliferation, angiogenesis, microvascular permeability and monocyte chemotaxis, the aim of this study was to clarify the relation of VEGF to the development of proteinuria in children with primary nephrotic syndrome. Thirty patient with primary nephrotic syndrome were included in the study. They were 16 males [53.33%] and 14 females [46.67%]. Their mean age was 5.57 +/- 3.3 years [range 1.5-12 years]. Also, 20 age-and sex-matched healthy children were included as controls. All of our patients were subjected to full clinical assessment, routine laboratory investigations focusing on Urinary 24-hour protein, and urinary albumin /creatinine ratio. VEGF was measured in serum samples using competitive enzyme immunoassay which measures the natural and recombinant forms of the cytokine VEGF. The results showed that serum VEGF concentration was significantly higher in the studied patients [179.8 +/- 85.4 pg/ml] compared to the controls [37.5 +/- 24.3 pg/ml] [p=0.006]. Significant positive correlations were found between VEGF and urinary albumin creatinine ratio [r0.737; p=0,001], and 24-hour urinary protein excretion [r0.735; p=0. 001]. Serum VEGF was significantly increased in children with first attack nephrotic syndrome [240.4 +/- 80.21 pg/ml] compared to those with a relapse [150.74 +/- 80.5 pg/ml] [p=0.005]. Also, those with steroid-sensitive nephrotic syndrome were found to have higher mean serum VEGF [205.44 +/- 70.41 pg/ml] than those with steroid-resistant nephrotic syndrome [105.37 +/- 80.76 pg/ml [p=0.003]
Conclusion: this study demonstrated high serum levels of VEGF in children with active primary nephrotic syndrome, and these levels were higher in steroid-sensitive patients than in steroid-resistant patients. Also, the levels were higher in first attack nephrotic than in relapsers. Thus, VEGF may be involved in the development of proteinuria in primary nephrotic syndrome. Further studies are recommended for better understanding of the pathophysiologic role of VEGF and if it might be related to a specific glomerular pathology