A recent survey found that approximately 4% of very low birth weight infants in Japan were treated with glucocorticoids postnatally for circulatory collapse thought to be caused by late-onset adrenal insufficiency. We identified 11 preterm infants with clinical signs compatible with this diagnosis (hypotension, oliguria, hyponatremia, lung edema, and increased demand for oxygen treatment) and matched them for gestational age with 11 infants without such signs. Blood samples were obtained for cortisol and its precursors from the patient group before the administration of hydrocortisone, and from the control group during the same postnatal week. All samples were analyzed using a gas chromatography-mass spectrometry system. Cortisol concentrations did not differ between the two groups (6.6 Ϯ 4.5 vs 3.4 Ϯ 2.7 g/dL); however, the total concentration of precursors in the pathway to cortisol production was significantly higher in the patient group (72.2 Ϯ 50.3 vs 25.0 Ϯ 28.5 g/dL; p Ͻ 0.05). We conclude that the clinical picture of late-onset adrenal insufficiency in preterm infants is not a result of an absolute deficiency of cortisol production, but may be a result of a limited ability to synthesize sufficient cortisol for the degree of clinical stress. A ccording to a recent nationwide survey in Japan, about 4% of very low birth weight (VLBW) infants are treated with postnatal steroids because of adrenal insufficiency of prematurity (AOP). This condition was defined in the survey as postnatal steroid usage during a hospital stay for treatment of late-onset circulatory collapse in premature infants (1). Reports on glucocorticoid-responsive hypotension among VLBW infants in the early postnatal period suggest that the hypothalamus-pituitary-adrenal system does not function sufficiently in the immediate postnatal period (2-7), and, as a result, the serum cortisol level is relatively low during the first week of life (8 -13). However, it has been suggested that this adrenal insufficiency in preterm infants is transient and that adrenal function tends to return to normal by the end of the second week of life (14). Two randomized control trials have demonstrated the benefit of glucocorticoids for preventing and treating refractory hypotension during the first week of life in VLBW infants (15,16). Therefore, glucocorticoid-responsive hypotension was not considered a common phenomenon beyond the first week of life in this population. However, VLBW infants sometimes develop late-onset glucocorticoid-responsive circulatory collapse.The purpose of the current study differs from previous reports on the above pathophysiological etiologies, because we focused specifically on late-onset circulatory instability, which is usually prominent after the first week of life in preterm infants. AOP was defined as postnatal steroid treatment for late-onset (after the first week of life) adrenal insufficiency in premature infants. To elucidate the pathogenesis of this disorder, a comparison of steroid hormone concentrations between ...
This combined navigations of fluorescence and 3-D imaging revealed more easy and effective to detect SLN intraoperatively than fluorescence imaging alone.
Receptor-operated Ca 2ϩ entry (ROCE) via transient receptor potential canonical channel 6 (TRPC6) is important machinery for an increase in intracellular Ca 2ϩ concentration triggered by the activation of G q protein-coupled receptors. TRPC6 is phosphorylated by various protein kinases including protein kinase A (PKA). However, the regulation of TRPC6 activity by PKA is still controversial. The purpose of this study was to elucidate the role of adenylate cyclase/cAMP/PKA signaling pathway in the regulation of G q protein-coupled endothelin type A receptor (ET A R)-mediated ROCE via TRPC6. For this purpose, human embryonic kidney 293 (HEK293) cells stably coexpressing human ET A R and TRPC6 (wild type) or its mutants possessing a single point mutation of putative phosphorylation sites for PKA were used to analyze ROCE and amino acids responsible for PKA-mediated phosphorylation of TRPC6. Ca 2ϩ measurements with thapsigargin-induced Ca 2ϩ -depletion/Ca 2ϩ -restoration protocol to estimate ROCE showed that the stimulation of ET A R induced marked ROCE in HEK293 cells expressing TRPC6 compared with control cells. The ROCE was inhibited by forskolin and papaverine to activate the cAMP/PKA pathway, whereas it was potentiated by Rp-8-bromoadenosinecAMP sodium salt, a PKA inhibitor. The inhibitory effects of forskolin and papaverine were partially cancelled by replacing Ser28 (TRPC6 S28A ) but not Thr69 (TRPC6 T69A ) of TRPC6 with alanine. In vitro kinase assay with Phos-tag biotin to determine the phosphorylation level of TRPC6 revealed that wild-type and mutant (TRPC6 S28A and TRPC6 T69A ) TRPC6 proteins were phosphorylated by PKA, but the phosphorylation level of these mutants was lower (approximately 50%) than that of wild type. These results suggest that TRPC6 is negatively regulated by the PKA-mediated phosphorylation of Ser28 but not Thr69.
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