Mashhad, Iran
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Sadeghian M.H.,Mashhad University of Medical Sciences | Keramati M.R.,Neonatal Research Center | Ayatollahi H.,Mashhad University of Medical Sciences | Rafatpanah H.,Immunology research center | Baesi N.,Mashhad University of Medical Sciences
Iranian Journal of Pathology | Year: 2011

Background and Objectives: Complement proteins are some of the most important plasma proteins of the innate immune system. Impaired immune function is reported in subjects who are iron deficient, and there are documents that these patients are prone to infection. This study was conducted to show whether serum C3 and C4 complement change in adult nonpregnant female with iron deficient anemia or not. Methods: Forty five normal subjects and 45 iron deficient anemia (hypochrom microcytic) cases were entered in this case and control study by using patients' clinical history and also results of CBC, Serum ferritin, iron and total iron binding capacity. Serum C3, and C4 were measured in case and control subjects with nephlometry method, finally comparison between result of patients group and control group was done with using suitable statistical test. Results: Mean serum C3 and C4 in patient group was 1.28 ± 0.81 and 0.28 ± 0.23 g/L respectively and for control group was 1.39 ± 0.87 and 0.35 ± 0.25 g/L respectively. Although serum complements were slightly lower in patient groups in compared to control group but this differences was not meaningful with t test. Conclusion: This study showed serum C3 and C4 complements levels were not changed in iron deficiency anemia.


Tara F.,Mashhad University of Medical Sciences | Rayman M.P.,University of Surrey | Boskabadi H.,Neonatal Research Center | Ghayour-Mobarhan M.,Avicenna Research Institute | And 13 more authors.
Journal of Perinatal Medicine | Year: 2010

Objective: We assessed the impact of selenium, a trace element with antioxidant properties on a simple measure of oxidative stress in pregnant women. Study design: A novel assay of prooxidant-antioxidant balance (PAB) was applied in a double-blind, placebo-controlled study of selenium supplementation in pregnancy. We measured the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby calculating a redox index. A total of 166 primigravid pregnant women in the first trimester of pregnancy, were randomized to receive 100 μg of selenium (n=83) or placebo (n=83) per day until delivery. PAB values and serum selenium concentrations were measured at baseline and at the end of study. Results: Pretreatment demographic data and biochemical indices including serum selenium concentrations did not differ significantly between the groups. The drop-out rates for the groups were 22/83 and 19/83 for the selenium and placebo groups, respectively. Supplementation with selenium was associated with a significant increase in mean serum selenium concentration (P<0.001) but without significant change in mean PAB value. In contrast, mean serum selenium concentration remained unchanged and mean PAB values increased significantly (P<0.05 in the control group). Conclusion: Our findings suggest that selenium supplementation may reduce oxidative stress associated with pregnancy. © 2010 by Walter de Gruyter Berlin New York.


PubMed | University of California at Los Angeles and Neonatal Research Center
Type: Clinical Trial | Journal: JPEN. Journal of parenteral and enteral nutrition | Year: 2015

Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure-associated liver disease (IFALD).This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/d) in 10 patients who were receiving most of their calories from parenteral nutrition (PN). Patients were compared with 20 historic controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk.The Kaplan-Meier method estimated that 75% in the FO group would experience resolution of cholestasis by 17 weeks vs 6% in the SO group (P < .0001). When compared with the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (P = .03) and 12, 16, 20, and 24 weeks (P < .0001). Although length z score at the end of the study increased in the FO group compared with baseline (P = .03), there were no significant differences in other outcomes.A limited duration of FO appears to be safe and effective in reversing IFALD.


Raychaudhuri N.,Neonatal Research Center | Raychaudhuri N.,University of Michigan | Thamotharan S.,Neonatal Research Center | Srinivasan M.,State University of New York at Buffalo | And 3 more authors.
Journal of Nutritional Biochemistry | Year: 2014

Early life nutritional intervention causes adult-onset insulin resistance and obesity in rats. Thyroid hormone receptor (TR), in turn, transcriptionally enhances skeletal muscle Glut4 expression. We tested the hypothesis that reduced circulating thyroid-stimulating hormone and T4 concentrations encountered in postnatal (PN4-PN24) high-carbohydrate (HC) milk formula-fed versus the mother-fed controls (MF) would epigenetically interfere with TR induction of adult (100. days) male rat skeletal muscle Glut4 expression, thereby providing a molecular mechanism mediating insulin resistance. We observed increased DNA methylation of the CpG island with enhanced recruitment of Dnmt3a, Dnmt3b and MeCP2 in the glut4 promoter region along with reduced acetylation of histone (H)2A.Z and H4 particularly at the H4.lysine (K)16 residue, which was predominantly mediated by histone deacetylase 4 (HDAC4). This was followed by enhanced recruitment of heterochromatin protein 1β to the glut4 promoter with increased Suv39H1 methylase concentrations. These changes reduced TR binding of the T3 response element of the glut4 gene (TREs; -473 to -450. bp) detected qualitatively in vivo (electromobility shift assay) and quantified ex vivo (chromatin immunoprecipitation). In addition, the recruitment of steroid receptor coactivator and CREB-binding protein to the glut4 promoter-protein complex was reduced. Co-immunoprecipitation experiments confirmed the interaction between TR and CBP to be reduced and HDAC4 to be enhanced in HC versus MF groups. These molecular changes were associated with diminished skeletal muscle Glut4 mRNA and protein concentrations. We conclude that early postnatal exposure to HC diet epigenetically reduced TR induction of adult male skeletal muscle Glut4 expression, uncovering novel molecular mechanisms contributing to adult insulin resistance and obesity. © 2014.


Calkins K.,Neonatal Research Center | Devaskar S.U.,Neonatal Research Center
Current Problems in Pediatric and Adolescent Health Care | Year: 2011

Dr. David Barker first popularized the concept of fetal origins of adult disease (FOAD). Since its inception, FOAD has received considerable attention. The FOAD hypothesis holds that events during early development have a profound impact on one's risk for development of future adult disease. Low birth weight, a surrogate marker of poor fetal growth and nutrition, is linked to coronary artery disease, hypertension, obesity, and insulin resistance. Clues originally arose from large 20th century, European birth registries. Today, large, diverse human cohorts and various animal models have extensively replicated these original observations. This review focuses on the pathogenesis related to FOAD and examines Dr. David Barker's landmark studies, along with additional human and animal model data. Implications of the FOAD extend beyond the low birth weight population and include babies exposed to stress, both nutritional and nonnutritional, during different critical periods of development, which ultimately result in a disease state. By understanding FOAD, health care professionals and policy makers will make this issue a high health care priority and implement preventive measures and treatment for those at higher risk for chronic diseases. © 2011 Mosby, Inc. All rights reserved.


Tarvij Eslami S.,Neonatal Research Center | Nassirian H.,Neonatal Research Center | Mojgan B.M.,Neonatal Research Center | Bahieh Z.Z.,Neonatal Research Center | And 3 more authors.
Pediatrics International | Year: 2012

Background: The aim of the present study was to evaluate the characteristics and accuracy of cerebrospinal fluid (CSF) parameters for neonatal meningitis, by comparing CSF data in newborns and in infants ≤2 months of age, with or without meningitis. Methods: This case-control study was performed on 120 newborns and infants a;circ2 months old. 60 patients with meningitis were considered as the case group and 60 ill patients without meningitis were defined as the control group. Each of the two groups was divided into 0-1 months and 1-2 months old. CSF characteristics were compared in newborns in the case and control groups; in infants ≤2 months old in the case and control groups; and in healthy newborns and healthy infants a;circ2 months old. Results: The mortality rate was 16.7% in the case group. The differences of CSF parameters in the case and control groups were mostly not significant, except for CSF glucose only in term newborns <7 days old (P= 0.04), and white cell count (WBC) only in 0-7-day-old term and preterm neonates (P= 0.04 and P= 0.01, respectively). Polymorphonuclear leukocyte (PMNL) level in the case group was significantly higher than in the control group (P= 0.02). CSF characteristics in healthy newborns were nearly the same as in healthy infants ≤2 months old. Prevalence of positive CSF culture was 31.7% in the case group. The most common pathogen was Neisseria meningitidis in the two age groups. The concomitant positive blood culture in the case group was 26.3%. Conclusion: In the case of meningitis with negative CSF culture and Gram stain, diagnosis can be made on CSF parameters, clinical and laboratory findings and suspicion of meningitis. Therefore, a clinical prediction rule to classify risk for bacterial meningitis on evaluation of CSF parameters in any region should be established. More regional trials are needed to enhance the probability of diagnosis according to CSF parameters. © 2011 Japan Pediatric Society.


Londhe V.A.,Neonatal Research Center | Tomi T.,Neonatal Research Center | Nguyen T.T.,Neonatal Research Center | Lopez B.,Neonatal Research Center | Smith J.B.,Neonatal Research Center
Developmental Dynamics | Year: 2015

Background: Lung maturation can be disrupted through pro-inflammatory processes including intra-uterine amniotic infection, mechanical ventilation, or oxidative stress. Lincr, originally identified as a gene induced in the lung by lipopolysaccharide (LPS), is also expressed in the developing lung. The Lung-inducible Neuralized-related C3HC4 RING domain (LINCR) protein is structurally related to Drosophila Neuralized, a regulator of the developmentally important Notch signaling pathway. LINCR is expressed in alveolar epithelial type II cells in the mature lung, and its expression is markedly increased by LPS and inflammatory cytokines. To test the hypothesis that targeted overexpression of LINCR in lung epithelium would interfere with normal lung development, we generated double transgenic mice that conditionally overexpress LINCR in lung epithelium under the control of doxycycline. Results: Single transgenic controls and double transgenic mice not treated with doxycycline were unaffected, but double transgenic mice exposed to doxycycline starting at embryonic day 6 developed markedly hypoplastic lungs with decreased numbers of alveoli and large cysts lined with a proximalized and poorly differentiated epithelium expressing Hairy/Enhancer of Split 1, an effector of Notch signaling. The phenotype was similar to that caused by overexpression of activated Notch1 in lung epithelium. Conclusions: LINCR may exert its effects on distal lung development in this model through activation of the Notch signaling pathway. © 2015 Wiley Periodicals, Inc.


Akbarzadeh M.,Shiraz University of Medical Sciences | Dokuhaki A.,Shiraz University of Medical Sciences | Joker A.,Shiraz University of Medical Sciences | Pishva N.,Neonatal Research Center | Zare N.,Shiraz University of Medical Sciences
Annals of Saudi Medicine | Year: 2016

BACKGROUND: Maternal-fetal attachment, which forms as soon as pregnancy starts, is essential to an infant's mental development. OBJECTIVE: This study aimed to explore the effect of teaching attachment behaviors to pregnant women on infant mental health from birth to 3 months of age. DESIGN: Randomized controlled trial. SETTING: Hafiz Hospital, Shiraz University of Medical Sciences, Iran, from February to November 2014. PATIENTS AND METHODS: The participants were randomly divided into an intervention and a control group at 28-34 weeks gestation. The participants in the intervention group attended six educational sessions each lasting for 60-90 minutes. After delivery, the infants of mothers in each group were compared in terms of mental health indexes (total mean scores and scores derived from a checklist of questions for infant mental health with results categorized as low, average and high). Maternal anxiety levels were also recorded at birth and at 3 months. MAIN OUTCOME MEASURE(S): Infant mental health index. RESULTS: In 190 pregnant women (96 in the intervention group and 94 in the control group), the total mean (SD) scores for infant mental health at birth were 16.66 (1.51) in the intervention group and 16.07 (1.74) in the control group (P=.013). At 3 months, the total mental health scores infants were 31.05 (1.88) in the intervention group and 30.25 (2.10) in the control group (P=.007). Differences in checklist scores between the groups at 3 months were not statistically significant, except for crying intensity at 3 months (P=.021). Women in the control group had higher anxiety levels at 3 months (P=.01). CONCLUSION: Teaching attachment skills to mothers increased the attachment between the mothers and their infants, and consequently, improved infant mental health. Thus, teaching attachment skills should be incorporated into routine prenatal care. LIMITATIONS: Use of phone calls by the researcher to assess mental health. © 2016, King Faisal Specialist Hospital and Research Centre. All rights reserved.


PubMed | Neonatal Research Center
Type: Journal Article | Journal: Journal of neuroscience research | Year: 2012

Energy balance is regulated by circulating leptin concentrations and hypothalamic leptin receptor (ObRb) signaling via STAT3 but is inhibited by SOCS3 and PTP1B. Leptin signaling enhances anorexigenic neuropeptides and receptor (POMC, MC3-R, MC4-R) activation while suppressing orexigenic neuropeptides (NPY, AgRP). We investigated in a sex-specific manner the early (PN2) and late (PN21) postnatal hypothalamic mechanisms in response to intrauterine (IUGR), postnatal (PNGR), and combined (IPGR) calorie and growth restriction. At PN2, both male and female IUGR were hypoleptinemic, but hypothalamic leptin signaling in females was activated as seen by enhanced STAT3. In addition, increased SOCS3 and PTP1B supported early initiation of leptin resistance in females that led to elevated AgRP but diminished MC3-R and MC4-R. In contrast, males demonstrated leptin sensitivity seen as a reduction in PTP1B and MC3-R and MC4-R with no effect on neuropeptide expression. At PN21, with adequate postnatal caloric intake, a sex-specific dichotomy in leptin concentrations was seen in IUGR, with euleptinemia in males indicative of persisting leptin sensitivity and hyperleptinemia in females consistent with leptin resistance, both with normal hypothalamic ObRb signaling, neuropeptides, and energy balance. In contrast, superimposition of PNGR upon IUGR (IPGR) led to diminished leptin concentrations with enhanced PTP1B and an imbalance in arcuate nuclear NPY/AgRP and POMC expression that favored exponential hyperphagia and diminished energy expenditure postweaning. We conclude that IUGR results in sex-specific leptin resistance observed mainly in females, whereas PNGR and IPGR abolish this sex-specificity, setting the stage for acquiring obesity after weaning.


PubMed | Neonatal Research Center
Type: Journal Article | Journal: Developmental dynamics : an official publication of the American Association of Anatomists | Year: 2015

Lung maturation can be disrupted through pro-inflammatory processes including intra-uterine amniotic infection, mechanical ventilation, or oxidative stress. Lincr, originally identified as a gene induced in the lung by lipopolysaccharide (LPS), is also expressed in the developing lung. The Lung-inducible Neuralized-related C3HC4 RING domain (LINCR) protein is structurally related to Drosophila Neuralized, a regulator of the developmentally important Notch signaling pathway. LINCR is expressed in alveolar epithelial type II cells in the mature lung, and its expression is markedly increased by LPS and inflammatory cytokines. To test the hypothesis that targeted overexpression of LINCR in lung epithelium would interfere with normal lung development, we generated double transgenic mice that conditionally overexpress LINCR in lung epithelium under the control of doxycycline.Single transgenic controls and double transgenic mice not treated with doxycycline were unaffected, but double transgenic mice exposed to doxycycline starting at embryonic day 6 developed markedly hypoplastic lungs with decreased numbers of alveoli and large cysts lined with a proximalized and poorly differentiated epithelium expressing Hairy/Enhancer of Split 1, an effector of Notch signaling. The phenotype was similar to that caused by overexpression of activated Notch1 in lung epithelium.LINCR may exert its effects on distal lung development in this model through activation of the Notch signaling pathway.

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