Journal of Pediatric Biochemistry - Volume 1, issue 3

Authors: Nilsson, Torbjörn K.

Article Type: Other

DOI: 10.3233/JPB-2010-0025

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 199-199, 2010

Authors: Krishnamoorthy, Malini | Gerwe, Brian A. | Heimburg-Molinaro, Jamie | Nash, Rachel J. | Arumugham, Jagan | Eilertson, Carmen D. | Stice, Steven L. | Nash, Rodney J.

Article Type: Research Article

Abstract: Ethanol consumption during pregnancy has been shown to promote abnormal development in offspring. These abnormalities include microcephaly, growth retardation, neurological deficits and behavioral and cognitive deficiencies. Cyclins and cyclin dependent kinases (CDKs) are crucial for cell cycle progression, proliferation and differentiation of various cell types. The purpose of our study was to better understand the effects of ethanol on proliferation during early human development by using three human embryonic stem cell (hESC) …lines. We found that treatment of ethanol at low doses (20 mM; four days) increased cell proliferation. The expression of key cell cycle regulators, CDKN2B (p15) and CDKN2A (p16) increased in two hESC lines, while CDKN1A (p21) and CDKN1B (p27) gene expression decreased in all cell lines. Western analysis showed a decrease in CDKN2B (p15) and CDKN2A (p16), while CDKN1A (p21) increased and CDKN1B (p27) remained unchanged. The changes in proliferation, gene expression, and protein synthesis suggest that ethanol can have a significant effect on cellular development at an early stage of human development. The correlation of our findings to in vivo conditions remains speculative, but the differential expression of regulators of the cell cycle may be involved in the manifestation of the many phenotypes seen in Fetal Alcohol Spectrum Disorder (FASD). Show more

Keywords: Human embryonic stem cell, proliferation, cell cycle proteins, ethanol, gene expression

DOI: 10.3233/JPB-2010-0026

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 201-208, 2010

Authors: Al Biltagi, Mohammed | Baset, Ahmed Abdul | Hagag, Adel | Al Srogi, Hesham

Article Type: Research Article

Abstract: The aim was to evaluate the serum leptin level in children with protein-energy malnutrition (PEM) with and without pneumonia. The study included 60 children; 20 were controls, 20 had PEM without infection and 20 had PEM and pneumonia. They were subjected to nutritional assessments; serum leptin level, haemoglobin concentration, white-blood cell (WBC) count, CD4%, serum albumin, blood glucose, blood urea-nitrogen, and serum ferritin, and chest x-ray. Serum leptin levels were independently associated with pneumonia on …multivariate analysis. In addition, serum leptin level and CD4% were significantly lower in the groups with PEM and pneumonia than in the group with PEM without pneumonia (p< 0.001). Low serum leptin levels were associated with pneumonia in children with protein energy malnutrition. Show more

Keywords: Protein-energy malnutrition, leptin, CD4%, marasmus, kwashiorkor

DOI: 10.3233/JPB-2010-0021

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 209-215, 2010

Authors: Mestan, Karen | Ouyang, Fengxiu | Matoba, Nana | Pearson, Colleen | Ortiz, Katherin | Wang, Xiaobin

Article Type: Research Article

Abstract: Infants born large-for-gestational age (LGA) are at risk for early childhood obesity. The aims of this study were to investigate factors associated with LGA status and their relationship to inflammatory biomarkers that have been implicated in the LGA infant at birth. Included were 364 mother-infant pairs enrolled as part of an ongoing longitudinal cohort study of infant birth weight being conducted at Boston Medical Center (BMC). LGA was defined as birth weight (BW) ⩾ 90th percentile …of the reference population at BMC (N=45). Appropriate-for-gestational age (AGA) was defined as BW<90th and >10th percentile (N=319). Cord blood IL-6, IL-8, TNF-alpha and RANTES levels were analyzed from a larger panel of immune biomarkers measured using multiplex immunoassay. Multivariate regression models were used to determine the associations between LGA status, maternal BMI and diabetes (DM), which included either gestational or type 2 diabetes (T2DM), and cord blood biomarkers, with adjustment for important demographic and clinical variables. Maternal pre-pregnancy BMI within the obesity range (⩾30 kg/m^{2} ), as well as DM, were each associated with increased risk of LGA (OR=2.64, 95%CI 1.31–6.20; OR=5.58, 95%CI 2.06–15.13, respectively). Among the 4 biomarkers, only RANTES (regulated on activation, normal T cell express and secreted upon uptake), which is a chemokine secreted by white adipose tissue, was significantly increased in LGA infants (beta-coefficient =0.37; 95%CI: 0.09, 0.65; P<0.01). This association remained essentially unchanged after adjustment for maternal DM and BMI (beta-coefficient=0.37; 95%: 0.08, 0.65; P=0.01). Ponderal index (PI=BWx100/length^{3} ) was also positively correlated with RANTES. Cord blood RANTES is selectively elevated with fetal macrosomia, independent of maternal factors. Further investigation of RANTES as a marker of LGA and future childhood health is warranted. Show more

Keywords: Birth weight, large-for-gestational age, cord blood, inflammation, obesity, diabetes

DOI: 10.3233/JPB-2010-0023

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 217-224, 2010

Authors: van der Watt, George F. | Eley, Brian | Henderson, Howard

Article Type: Research Article

Abstract: Nucleoside reverse transcriptase inhibitors (NRTIs) affect mitochondrial DNA polymerase gamma causing significant toxic effects, including fatal lactic acidosis. Little is known about mitochondrial DNA (mtDNA) in human immunodeficiency virus (HIV) infected children who face a lifetime exposure to these agents. We performed a cross sectional observation of mtDNA levels in whole blood in a pediatric population to ascertain the relationship between mtDNA, NRTI regimens and parameters of HIV-infection severity. Whole blood mitochondrial …/ nuclear DNA (mt:nDNA) ratios were determined by real-time PCR in three groups: 27 presumed HIV-negative, 89 HIV-infected, NRTI-treated and 62 HIV-infected treatment-naive children. Multivariate analysis was used to identify variables independently associated with mtDNA depletion. Mean mt:nDNA ratios were lower (p< 0.001) at 77% of control in the HIV-infected antiretroviral treatment (ART) naïve group and 73% of control in the ART group, but not different between the two HIV-infected groups. Mt:nDNA ratios were negatively associated with age (p=0.029), HIV status (p< 0.0001) and Log_{10} of the HIV-1 viral load (p=0.035) and positively associated with CD4% (p= 0.032). A stavudine vs. zidovudine based regimen was associated with lower but not significant levels of mtDNA (p=0.08). Depletion of whole blood mtDNA in children is associated independently with HIV-infection and markers of HIV infection severity, and does not improve with either stavudine or zidovudine based ART despite virological control, suggesting that these agents also deplete mtDNA. The long-term consequences of this potentially toxic effect remain a cause for concern Show more

Keywords: Pediatric HIV, NRTI's, mitochondrial toxicity, mitochondrial DNA depletion, DNA polymerase gamma

DOI: 10.3233/JPB-2010-0022

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 225-232, 2010

Authors: Chesney, Russell W.

Article Type: Research Article

Abstract: It has become apparent that large segments of the population have vitamin D deficiency or insufficiency. This is of concern because vitamin D has biologic actions that influence immunity, inflammation, and oncogenesis in more than 30 tissues types with vitamin D receptors. Vitamin D deficiency has been associated with numerous disorders, including diabetes, rheumatoid arthritis, multiple sclerosis, and several types of cancer. Sufficient circulating levels of vitamin D are critical not only for healthy bones, but …for many aspects of human health. The maintenance of adequate body stores of vitamin D depends on exposure to sunlight and dietary intake. Cutaneous synthesis of vitamin D and safe levels of dietary supplementation are discussed. Show more

Keywords: Vitamin D, vitamin D deficiency, cathelicidin, immunomodulation, vitamin D supplementation

DOI: 10.3233/JPB-2010-0024

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 233-237, 2010

Authors: Caylak, Emrah

Article Type: Research Article

Abstract: There is increasing evidence that biochemistry, genetics and cognitive deficits play a part in the etiology of developmental dyslexia (DD). The developmental dyslexia\reading disability (RD) that is part of a larger heterogeneous group of learning disorders, and characterized by unexpected problems in academic performance, despite average intelligence. However, controversy still surrounds both the identification and management of this condition, and while its etiology is recognized as being complex and multifactorial, yet little …progress has been made in elucidating predisposing factors at the biological level. The purpose of this review is to explore the possibility of dyslexia that falls within biochemical and cognitive spectrum of disorder. Based on the biochemical evidence, there is a necessity for further research into the role of fatty acids in developmental dyslexia that contributed with an abnormal metabolism of HUFA in fetal brain development, or the maintenance of normal brain function. Currently, the molecular geneticists have been seeking to identify the actual genes underlying developmental dyslexia. Nine loci were found to be associated with susceptibility to dyslexia (DYX1 to DYX9). Those have contained important four candidate genes associated with dyslexia that would aid in distinguishing between children whose reading problems are caused primarily by cognitive deficits with biological origin. Accordingly, the cognitive deficits of dyslexia will be presented in the domains of phonological, auditory processing, visual, magnocellular and automaticity/cerebellar deficit theories. Understanding the biochemical and cognitive basis of dyslexia may help us plan our future research. Show more

Keywords: Dyslexia, biochemistry, cognitive, phonological, auditory, visual, magnocellular, automaticity/cerebellar, multifactorial deficit model

DOI: 10.3233/JPB-2010-0020

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 239-268, 2010

Authors: Butenandt, Otfrid

Article Type: Research Article

Abstract: Normal growth of children depends on genetic background, normal nutrition, health, undisturbed endocrine system and a favorable environment as well as on psychosocial wellbeing. In case of growth disturbance, all negative influences must be removed. Endocrine therapy includes growth hormone, thyroid hormone or even sexual steroids.

Keywords: Growth of children, disturbance of growth, therapy of growth disorders

DOI: 10.3233/JPB-2010-0019

Citation: Journal of Pediatric Biochemistry, vol. 1, no. 3, pp. 269-275, 2010