Maternal glucocorticoids increase endotoxin-induced lung inflammation in preterm lambs

Antenatal betamethasone (Beta) is widely used in women with asymptomatic chorioamnionitis at risk for preterm delivery, but its effects on fetal inflammation are unstudied. Groups of ewes at 109 +/- 1 days of gestation received the following treatments: intra-amniotic (IA) saline (control), 0.5 mg/kg intramuscular Beta, 10 mg IA endotoxin (Endo), and Beta + 2 h later Endo (Beta + Endo). Beta suppressed Endo-induced lung inflammation at 1 day. However, compared with Endo 5 days after treatment, Beta + Endo lambs had increased alveolar neutrophils, proinflammatory cytokine mRNA expression, and serum amyloid A3 (SAA3) mRNA expression. IL-1beta mRNA expression was localized to the inflammatory cells, whereas SAA3 mRNA expression was induced in the bronchial epithelium and the inflammatory cells. Compared with Endo, Beta + Endo lambs had increased lung inflammation but equivalent lung volumes 15 days after treatment. The late increase in inflammation in the Beta + Endo animals suggests that glucocorticoids impair the ability of the preterm lung to downregulate Endo-induced inflammation after fetal clearance of the glucocorticoids. These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids.     

Studies on the mechanism by which glutamine and heat shock increase lactate synthesis by L929 cells in the presence of insulin

Both glutamine and heat shock increase lactate production in the L929 cell system. Glutamine is now shown to increase hexose uptake in the presence of insulin, to inhibit pyruvate oxidation, and to provide reducing equivalents to the cytosolic compartment. The relative contribution of these processes to lactate production depends on the availability of pyruvate. When ample pyruvate is available from the culture medium, stimulation of lactate synthesis by glutamine and heat shock is transaminase dependent, suggesting that shuttling of reducing equivalents from mitochondria to cytoplasm is involved. In the absence of medium pyruvate, stimulation of glycolysis by both glutamine and heat shock is largely responsible for increased lactate synthesis. None of the observed effects of glutamine appears to be sufficient to explain the observed stimulation of glycolysis.     

Studies on the mechanism of obstructive sleep apnea

Several observations indicate that the mylohyoid nerve (NV) may play a crucial part in the mechanisms of obstructive sleep apnea (OSA). The activity of this nerve normally counteracts the collapse of the upper airways during inspiration. Any reduction in this activity may thus facilitate the occurrence of apnoeic spells. We have studied the effects of ethanol and lung inflations on the activity of NV recorded along with the activities of phrenic and facial nerve in rabbits anaesthetised with chloralose-urethan, paralyzed with curare and artificially ventilated. Under the control conditions the NV exhibited phasic expiratory activity; after vagotomy and additional, inspiratory component was observed. Lung inflation strongly enhanced the expiratory activity of NV whereas both the phrenic and facial nerve activities (both phasic-inspiratory) were typically inhibited. An injection of 5 ml of 20% ethanol very strongly inhibited the NV activity. The results may confirm the importance of NV in the mechanism of OSA. The well-known fact that OSA patients are particularly sensitive to alcohol finds support in the response of NV activity to ethanol injection. The analysis of the patterns of discharges of the three outputs from the respiratory controller may additionally suggest that the Vth nerve nucleus is involved in the control of respiratory pattern.