A 5‐HT2A/2C receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane,mitigates developmental neurotoxicity of ethanol to serotonergic neurons

Prenatal ethanol exposure causes the reduction of serotonergic (5‐HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5‐HT_2A and 5‐HT_2C receptors during the fetal period is able to prevent the reduction of 5‐HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague–Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair‐fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), an agonist for 5‐HT_2A/2C receptors, during GDs 13 to 19 (Et‐DOI or Pf‐DOI), and another was injected with saline vehicle only (Et‐Sal or Pf‐Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5‐HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5‐HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et‐Sal fetuses compared to that of the Pf‐Sal and Pf‐DOI fetuses, whereas there were no significant differences between Et‐DOI and each Pf control. Thus, we concluded that the reduction of 5‐HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5‐HT_2A/2C receptors during the fetal period.     

Optimal birth weight percentile cut‐offs in defining small‐ or large‐for‐gestational‐age

Aims: It remains questionable what birth weight for gestational age percentile cut‐offs should be used in defining clinically important poor or excessive foetal growth. We aimed to evaluate the optimal birth weight percentile cut‐offs for defining small‐ or large‐for‐gestational‐age (SGA or LGA). Methods: In a birth cohort‐based analysis of 17 979 120 non‐malformation singleton live births, U.S. 1995–2001, we assessed the optimal birth weight percentile cut‐offs for defining SGA and LGA. The 25th–75th percentile group served as the reference. Primary outcomes are the risk ratios (RR) of neonatal death and low 5‐min Apgar score (<4) comparing SGA or LGA versus the reference group. More than 2‐fold risk elevations were considered clinically significant. Results: The 15th birth weight cut‐off already identified SGA infants at more than 2‐fold risk of neonatal death at pre‐term, term or post‐term, except for extremely pre‐term births <28 weeks (continuous risk reductions over increasing birth weight percentiles). LGA was associated with a reduced risk of low 5‐min Apgar score at pre‐term, but an elevated risk at term and post‐term. The 97th cut‐off identified LGA infants at 2‐fold risk of low 5‐min Apgar at term. Conclusion: The commonly used 10th and 90th birth weight percentile cut‐offs for defining SGA and LGA respectively seem largely arbitrary. The 15th and 97th percentiles may be the optimal cut‐offs to define SGA and LGA respectively.     

Maternal selenium,copper and zinc concentrations in pregnancy associated with small‐for‐gestational‐age infants

Pregnancy during adolescence increases the risk of adverse pregnancy outcome, especially small‐for‐gestational‐age (SGA) birth, which has been linked to micronutrient deficiencies. Smoking has been shown to be related to lower micronutrient concentrations. Different ethnicities have not been examined. We used a subset from a prospective observational study, the About Teenage Eating study consisting of 126 pregnant adolescents (14–18‐year‐olds) between 28 and 32 weeks gestation. Micronutrient status was assessed by inductively coupled mass spectrometry. Smoking was assessed by self‐report and plasma cotinine, and SGA was defined as infants born <10th corrected birthweight centile. The main outcome measures were as follows: (1) maternal plasma selenium, copper and zinc concentrations in adolescent mothers giving birth to SGA vs. appropriate‐for‐gestational‐age (AGA) infants; and (2) comparison of micronutrient concentrations between women of different ethnicities and smoking habits. The plasma selenium {mean ± standard deviation (SD) [95% confidence interval (CI)]} concentration was lower in the SGA [n = 19: 49.4 ± 7.3 (CI: 45.9, 52.9) µg L^?1] compared with the AGA [n = 107: 65.1 ± 12.5 (CI: 62.7, 67.5) µg L^?1; P < 0.0001] group. Smoking mothers had a lower selenium concentration compared with non‐smokers (P = 0.01) and Afro‐Caribbean women had higher selenium concentrations compared with White Europeans (P = 0.02). Neither copper nor zinc concentrations varied between groups. Low plasma selenium concentration in adolescent mothers could contribute to the risk of delivering an SGA infant, possibly through lowering placental antioxidant defence, thus directly affecting fetal growth. Differences in plasma selenium between ethnicities may relate to variation in nutritional intake, requiring further investigation.     

Interleukin‐6, interleukin‐8, interleukin‐11, and interferon‐γ levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)‐6, IL‐8, IL‐11, and interferon‐γ (IFN‐γ) levels in nasopharyngeal aspirates (NPA) from non‐asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL‐11 in NPA from asthmatic children were significantly higher than those from non‐asthmatic children with RSV infection, and RSV infection enhanced the IL‐11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL‐6 than that of children with IFAV infection. There was little difference in the IL‐8 and IFN‐γ levels between asthmatic and non‐asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL‐11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL‐6 production in RSV infection compared with IFAV infection.     

Determination of T‐cell subpopulations and intracellular cytokine production (interleukin‐2, interleukin‐4, and interferon‐γ) by cord blood T‐lymphocytes of neonates from atopic and non‐atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3⁺ CD4⁺ (Th lymphocytes), CD3⁺ CD8⁺ (T‐suppressor/cytotoxic lymphocytes), CD19⁺ (B lymphocytes), CD3⁺ CD4⁺ CD45RO⁺ (memory Th lymphocytes), and CD3⁺ CD4⁺ CD45RA⁺ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.     

Thrombocytopenia‐associated multi‐organ failure secondary to hyperglycemic,hyperosmolar non‐ketotic syndrome: A case report

Thrombocytopenia associated multi‐organ failure (TAMOF) is a clinical syndrome with features of new onset thrombocytopenia, increased lactate dehydrogenase, and multi‐organ failure in critically ill patients. TAMOF can be the initial presentation of an underlying disease process or can develop during the course of illness either during the hospital stay. TAMOF has a high mortality rate if not treated; therefore, early detection is critical. TAMOF has been rarely reported in diabetic ketoacidosis. We are describing the first case of a patient diagnosed with hyperglycemic, hyperosmolar non‐ketotic syndrome who developed TAMOF on the third day of his hospital course. In addition to supportive care in the intensive care unit the patient received serial therapeutic plasma exchanges and improved quickly after treatment. Early diagnosis and treatment of TAMOF decreases morbidity and mortality.     

Neonatal cholestasis and glucose‐6‐P‐dehydrogenase deficiency

We report a Caucasian neonate with chronic non‐spherocytic hemolytic anemia due to a class I G6PD deficiency. A novel mutation missense mutation in exon eight of the G6PD gene was detected (c.827C>T p.Pro276Leu). Bilirubin peaked on day 5 at 24 mg/dl with a conjugated bilirubin of 17 mg/dl. Jaundice resolved within 4 weeks. A detailed work‐up failed to reveal other specific factors contributing to cholestasis. Severe hemolytic disease of the newborn may cause cholestasis even in the absence of associated primary hepato‐biliary disease. Pediatr Blood Cancer 2010;54:758–760. © 2010 Wiley‐Liss, Inc.