Myxoma viral serpin, Serp-1, a unique interceptor of coagulation and innate immune pathways

Serpins maintain haemostasis through regulation of serine proteinases in the thrombotic and thrombolytic pathways. Viruses encode serpins that can alter thrombotic and thrombolytic responses producing, in some cases, disseminated intravascular coagulation (DIC). However, it has not been precisely defined how viral serpins induce these profound responses. The rabbit myxoma viral serpin, Serp-1 inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA), plasmin and factor Xa in vitro and exhibits remarkable anti-inflammatory activity in various animal models. The effects of Serp-1 on activation of human platelets, endothelial cells, monocytes and T cells that mediate thrombosis and innate immune responses were therefore examined. We found that Serp-1 attenuated platelet and mononuclear cell adhesion to fibronectin and collagen. Serp-1 similarly inhibited monocyte migration into the peritoneum. Serp-1 inhibition of monocyte migration was lost in uPA receptor (uPAR) deficient mice. Serp-1 bound to the plasma membrane surface and altered uPA activation of endothelial cells (p=0.001), thrombin activation of platelets (p=0.021) and phorbol ester activation of endothelial (p=0.047), monocyte (p=0.011) and Jurkat T cells (p=0.012) as measured by intracellular calcium. Modulation of cellular activation was confirmed by membrane fluidity analysis. Microarray analysis of Serp-1 treated endothelial cells revealed alterations in Inositol 1,4,5-triphosphate receptor type II (ITPR2) a calcium-regulating gene. This study demonstrates the unique capacity of a viral serpin, Serp-1 to modify adhesion, activation, gene expression and calcium homeostasis in a wide range of cells that regulate coagulation and inflammation. Endothelial cells potentially represent a pivotal regulatory point for Serp-1 anti-inflammatory activity.     

N-terminal-pro-brain natriuretic peptide: a guide for early targeted indomethacin therapy for patent ductus arteriosus in preterm Infants

Aim: To determine whether N‐terminal‐pro‐brain natriuretic peptide (NT‐proBNP) level could be an effective guide for early targeted indomethacin therapy for patent ductus arteriosus (PDA) in preterm infants. Methods: An interventional study involved preterm infants, born at <33 weeks of gestation, who had plasma NT‐proBNP levels obtained at day 2 of life. Indomethacin therapy was given if plasma NT‐proBNP level was ≥10 180 pg/mL, the cut‐off for predicting hemodynamic significant PDA (hsPDA). Echocardiograms were performed within 6 h at the time of plasma NT‐proBNP collection and again at day 7, or whenever clinical hsPDA was suspected. Primary outcomes were the incidence of later hsPDA and unnecessary exposure rate to indomethacin. Results: Fifty infants were enrolled. On day 2, 19 (38%) infants had plasma NT‐proBNP above the cut‐off and received indomethacin therapy; none of them developed later hsPDA, while 1 of 31 infants with NT‐proBNP below the cut‐off level developed clinical hsPDA. Unnecessary exposure to indomethacin occurred in two infants (11%). Overall, no enrolled infants had either reopening of ductus or PDA ligation. Conclusion: Using NT‐proBNP level on day 2 as a guide for early targeted indomethacin therapy reduced later onset of hsPDA and the number of unnecessary exposures to indomethacin.     

Comparison of television viewing between children with autism spectrum disorder and controls

Aim: To examine the pattern and extent of television viewing in children with autism spectrum disorder (ASD) compared with typically developing controls and those with delayed language development (DLD). Methods: Fifty‐four individuals with ASD (mean age 2.56 ± 0.66 years) and 84 controls (mean age 2.43 ± 0.81 years) were enrolled. Fifty‐six individuals with DLD, who had language developmental levels similar to those with ASD, were enrolled in our previous study. Main outcome measures included onset and frequency of television viewing, in addition to the type of programme and whether a caregiver cowatched television. Results: Those with ASD began to watch television significantly earlier than controls (6.44 ± 6.35 vs. 12.41 ± 6.00 months of age, p ≤ 0.0001*) and spent more time watching television than those with DLD (4.60 ± 1.91 vs. 3.05 ± 1.90 h/day, p ≤ 0.0001*) and controls (4.60 ± 1.91 vs. 2.06 ± 1.21 h/day, p ≤ 0.0001*). Those with ASD appeared to watch more adult programmes than normal controls, and they were less likely to watch television with caregivers than both control groups. Conclusion: There is an earlier onset and higher frequency of television viewing in autistic children compared with children with typical development.     

Neonatal infections in Asia

OBJECTIVE: To study the epidemiology (including incidence, antibiotic sensitivity and mortality) of neonatal unit infections in countries in Asia. METHODS: One year prospective study of neonatal infections in eight neonatal units in Asia. RESULTS: There were 453 episodes of sepsis affecting 394 babies. Mortality from neonatal sepsis was 10.4%, with an incidence of 0.69 deaths/1000 live births. Group B streptococcus was the most common early-onset organism causing 38% of episodes of early-onset (<48 h old) sepsis, with a rate of 0.51 episodes per 1000 live births and a mortality of 22%. Gram-negative bacillary early-onset sepsis occurred at a rate of 0.15 episodes per 1000 live births with a mortality of 12%. There were 406 episodes of late-onset sepsis. The incidence was high at 11.6 per 1000 live births, and mortality was 8.9%. Coagulase-negative staphylococcus caused 34.1% of episodes, whereas Staphylococcus aureus caused only 5.4%. Gram-negative bacilli caused 189 episodes (46.6%). Only 44% of Gram-negative bacilli were sensitive to both gentamicin and a third-generation cephalosporin, whereas 30% were resistant to both antibiotics. Meningitis occurred in 17.2% of episodes of late sepsis, with a mortality of 20%. CONCLUSIONS: The incidence of late-onset sepsis was higher in Asia than in resource-rich countries, but the organisms isolated and mortality were similar. Over half of all Gram-negative bacilli were antibiotic resistant.     

Efficacy of oral erythromycin for treatment of feeding intolerance in preterm infants

OBJECTIVE: To determine the efficacy and safety of oral erythromycin (EM) for feeding intolerance in preterm infants < 35 weeks gestation. STUDY DESIGN: In this randomized, double-blinded, placebo-controlled trial, preterm infants with feeding intolerance were randomly allocated to a treatment group given EM ethyl succinate 10 mg/kg every 6 hours for 2 days, followed by 4 mg/kg every 6 hours for another 5 days, or to a control group given placebo. The primary outcome was time to full feeding (150 mL/kg/day) after the start of treatment. RESULTS: Each group comprised 23 preterm infants, almost all of whom were < 32 weeks gestation. Baseline characteristics were similar between the 2 groups. Times to full feeding were significantly shorter and the number of withheld feeds were significantly less in the EM group than the control group; the respective medians (interquartile ranges) were 7 days (6 to 9 days) versus 13 days (9 to 15 days) (P < .001) and 1 episode (0 to 2 episodes) versus 9 episodes (2 to 13 episodes) (P < .001). No significant differences in episodes of sepsis, necrotizing enterocolitis, and cholestasis were observed. CONCLUSIONS: Oral EM was effective and safe for treatment of feeding intolerance in preterm infants.     

Echocardiographic parameters of patent ductus arteriosus in preterm infants

Objective  

To analyze cardiovascular parameters by echocardiography in preterm infants with patent ductus arteriosus (PDA).