BackgroundPregnant women at a high risk of preterm delivery receive glucocorticoids to accelerate fetal lung maturation and surfactant synthesis. However, the effect of antenatal steroids on the developing diaphragm remains unclear. We hypothesized that maternal betamethasone impairs the fetal diaphragm, and the magnitude of the detrimental effect increases with longer duration of exposure. We aimed to determine how different durations of fetal exposure to maternal betamethasone treatment influence the fetal diaphragm at the functional and molecular levels.MethodsDate-mated merino ewes received intramuscular injections of saline (control) or two doses of betamethasone (5.7 mg) at an interval of 24 h commencing either 2 or 14 days before delivery. Preterm lambs were killed after cesarean delivery at 121-day gestational age. In vitro contractile measurements were performed on the right hemidiaphragm, whereas molecular/cellular analyses used the left costal diaphragm.ResultsDifferent durations of fetal exposure to maternal betamethasone had no consistent effect on the protein metabolic pathway, expression of glucocorticoid receptor and its target genes, cellular oxidative status, or contractile properties of the fetal lamb diaphragm.ConclusionThese data suggest that the potential benefits of betamethasone exposure on preterm respiratory function are not compromised by impaired diaphragm function after low-dose maternal intramuscular glucocorticoid exposure.
1 Candoxin (MW 7334.6), a novel toxin isolated from the venom of the Malayan krait Bungarus candidus, belongs to the poorly characterized subfamily of nonconventional three-finger toxins present in Elapid venoms. The current study details the pharmacological effects of candoxin at the neuromuscular junction. 2 Candoxin produces a novel pattern of neuromuscular blockade in isolated nerve-muscle preparations and the tibialis anterior muscle of anaesthetized rats. In contrast to the virtually irreversible postsynaptic neuromuscular blockade produced by curaremimetic alpha-neurotoxins, the neuromuscular blockade produced by candoxin was rapidly and completely reversed by washing or by the addition of the anticholinesterase neostigmine. 3 Candoxin also produced significant train-of-four fade during the onset of and recovery from neuromuscular blockade, both, in vitro and in vivo. The fade phenomenon has been attributed to a blockade of putative presynaptic nicotinic acetylcholine receptors (nAChRs) that mediate a positive feedback mechanism and maintain adequate transmitter release during rapid repetitive stimulation. In this respect, candoxin closely resembles the neuromuscular blocking effects of d-tubocurarine, and differs markedly from curaremimetic alpha-neurotoxins that produce little or no fade. 4 Electrophysiological experiments confirmed that candoxin produced a readily reversible blockade (IC(50) approximately 10 nM) of oocyte-expressed muscle (alphabetagammadelta) nAChRs. Like alpha-conotoxin MI, well known for its preferential binding to the alpha/delta interface of the muscle (alphabetagammadelta) nAChR, candoxin also demonstrated a biphasic concentration-response inhibition curve with a high- (IC(50) approximately 2.2 nM) and a low- (IC(50) approximately 98 nM) affinity component, suggesting that it may exhibit differential affinities for the two binding sites on the muscle (alphabetagammadelta) receptor. In contrast, curaremimetic alpha-neurotoxins have been reported to antagonize both binding sites with equal affinity.