Objective Circulating blood cells and endothelial cells express Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5’-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine. The goal of this study was to examine the interplay between CD39 and CD73 cascade in arterial thrombosis. Approach and Results To determine how CD73 activity influences in vivo thrombosis, the time to FeCl3-induced arterial thrombosis was measured in CD73-null mice. In response to 5% FeCl3, but not to 10% FeCl3, there was a significant decrease in the time to thrombosis in CD73-null mice compared to wild-type (WT) mice. In mice overexpressing CD39, ablation of CD73 did not inhibit the prolongation in the time to thrombosis conveyed by CD39 overexpression. However, the CD73 inhibitor α-β-methylene-ADP nullified the prolongation in the time to thrombosis in hC39-Tg/CD73-null mice. To determine if hematopoietic-derived cells or endothelial cell CD39 activity regulates in vivo arterial thrombus, bone marrow transplant studies were conducted. FeCl3-induced arterial thrombosis in chimeric mice revealed a significant prolongation in the time to thrombosis in hCD39-Tg reconstituted WT mice, but not on WT reconstituted hCD39-Tg mice. Monocyte depletion with clodronate-loaded liposomes normalized the time to thrombosis in hCD39-Tg mice compared to hCD39-Tg mice treated with control liposomes, demonstrating that increased CD39 expression on monocytes protects against thrombosis. Conclusions These data demonstrate that ablation of CD73 minimally effects in vivo thrombosis, but increased CD39 expression on hematopoietic-derived cells, especially monocytes, attenuates in vivo arterial thrombosis.
Therapeutic hypothermiaHearing impairment a b s t r a c t Objective: To establish the local incidence of hearing loss in newborns with Hypoxic Ischaemic Encephalopathy (HIE) and to identify associated risk factors.Study design: Retrospective Cohort Study. Neonatal Intensive Care Unit (NICU) dual stage hearing screening protocol, including automated otoacoustic emissions (AOAE) and automated auditory brainstem response (AABR) testing.Results: 57 newborns received therapeutic hypothermia for HIE. Twelve babies (21%) died.Audiology data was incomplete in 3 babies. Complete data was available for 42 babies (male n ¼ 24), 4 (9.5%) of whom had hearing impairment. The development of hearing loss was associated with abnormal blood glucose levels (p ¼ 0.006), low Apgar score at 1 min (p ¼ 0.0219) and evidence of multi organ dysfunction [high creatinine (p ¼ 0.0172 and 0.0198) and raised liver transaminases (aspartate aminotransferase (AST) p ¼ 0.0012, alanine aminotransferase (ALT) p ¼ 0.0037)]. An association with gentamicin was not found.Conclusion: This study confirms that hearing impairment is common in term infants who have undergone therapeutic hypothermia for moderate/severe HIE. Blood glucose should be monitored carefully in these infants and developmental surveillance should include formal audiology. Further larger studies are needed to clarify the role, if any, of hypothermia per se in causation of hearing loss and to fully identify risk factors for hearing impairment in this population. What is new:The current study confirms that hearing impairment is common in term infants who have undergone therapeutic hypothermia for moderate/severe HIE.No association between gentamicin use and the development of hearing impairment was found however initial blood glucose outside the normal range was of significance.Other factors associated with hearing impairment were low Apgar scores, greater need for resuscitation and evidence of multi organ dysfunction (renal and liver failure).
We report a case of transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake in pregnancy. Vitamin D insufficiency and deficiency in pregnancy are associated with adverse pregnancy outcomes, but there is no definite benefit to supplementation. The Royal College of Obstetrics and Gynaecology recommends routine supplementation with vitamin D 400 IU/day, but higher dose preparations usually recommended for the treatment of vitamin D deficiency are readily available over the counter. This case highlights the risks of excess supplementation, especially at higher doses and in women without evidence of vitamin D deficiency. The amount used in this case was at the upper end of the generally accepted safe dose range, but still less than that commonly recognised to cause problems. Neonatal hypercalcaemia is a potentially serious condition. The current local or national recommendations for vitamin D supplementation and the possible adverse effects of excess vitamin D consumption should be clearly communicated to pregnant women.
In the bolus only group, the highest mean Mg levels were observed with administration 1-2 hours before delivery, but the findings were not statistically significant. Compared to the rest of the cohort, higher Mg levels were found when a bolus was followed by an infusion. Following a MgSO bolus, some growth restricted extremely preterm babies may have higher Mg levels than would be otherwise expected.
Background Increased uterine activity (UA) may not allow adequate recovery time for foetal oxygenation. Methods The aim of the study was to determine if increased UA during labour is associated with an increased risk of either short- or long-term neurological injury in term neonates, or with neonatal proxy measures of intrapartum hypoxia-ischemia. MEDLINE, CINAHL, and ClinicalTrials.gov were searched using the following terms: uterine activity, excessive uterine activity, XSUA, uterine hyperstimulation, and tachysystole. Any study that analysed the relationship between UA during term labour and neurological outcomes/selected proxy neurological outcomes was eligible for inclusion. Outcomes from individual studies were reported in tables and presented descriptively with odds ratios (OR) and 95% confidence intervals (CI) for dichotomous outcomes and means with standard deviations for continuous outcomes. Where group numbers were provided, ORs and their CIs were calculated according to Altman. Main results Twelve studies met the inclusion criteria. Seven studies featured umbilical artery pH as an individual outcome. Umbilical artery base excess and Apgar scores were both reported as individual outcomes in four studies. No study examined long term neurodevelopmental outcomes and only one study reported on encephalopathy as an outcome. The evidence for a relationship between UA and adverse infant outcomes was inconsistent. The reported estimated effect size varied from non-existent to clinically significant. Conclusions There is some evidence that increased UA may be a non-specific predictor of depressed neurological function in the newborn, but it is inconsistent and insufficient to support the conclusion that an association generally exists.
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