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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent Consensus Conference endorsed antenatal steroid use in prematurity, but indicated the need for future work on molecular and cellular effects on the developing brain. In the current study, pregnant rats were given dexamethasone during late gestation, in doses spanning those recommended for use, and effects on nuclear transcription factors were evaluated. Within the first hour after a single dose of dexamethasone, and intensifying over 4 h, marked induction of brain c-fos was seen. With repeated administration, c-fos became suppressed in some brain regions, but remained elevated in others. Dexamethasone also elicited suppression of the AP-1 family of nuclear binding proteins, but with a slower time course than seen for c-fos induction. The magnitude of the effects of late gestational exposure to dexamethasone on these transcription factors was comparable to those seen when repeated doses were administered to midgestation embryos in the context of dysmorphogenesis. Similarly, the effects on brain c-fos expression were substantially greater than those in the liver, an archetypal glucocorticoid target tissue. These results indicate that even a single, low dose of glucocorticoids used in late gestation, can disrupt the transcription factors that regulate brain cell differentiation.
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PMID:Glucocorticoid administration alters nuclear transcription factors in fetal rat brain: implications for the use of antenatal steroids. 980 69

Dexamethasone is used commonly in the treatment of chronic lung disease of prematurity, but there are concerns about possible deleterious effects on growth and bone. Our aim in this study was to examine the effects of dexamethasone treatment on bone and collagen turnover in preterm infants. Bone-specific alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP, reflecting whole-body type I collagen synthesis), and the N-terminal propeptide of type III procollagen (P3NP, reflecting soft tissue collagen turnover), together with the C-terminal telopeptide of type I collagen (ICTP), urinary pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown) were measured at weekly intervals over the first 12 wk of life in 14 preterm infants with chronic lung disease treated with dexamethasone. Results were expressed as SD scores relative to preterm control infants not treated with dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (-2.1 to -3.7 SD scores) during the first week of treatment (p < 0.001), returning to pretreatment levels after stopping dexamethasone. In the group as a whole, these collagen markers were negatively correlated with dexamethasone dose (p < 0.0001); negative correlations were also seen in most individual babies, although the slopes of individual regression lines varied by a factor of 2. Weight gain at 12 wk was correlated with PICP, expressed as the mean SD score over 12 wk for each baby, (r = 0.69, p < 0.01) but not with other markers or cumulative dose of dexamethasone. We conclude that dexamethasone markedly suppressed collagen turnover in preterm infants in a dose-dependent fashion, although some babies were more affected than others. The degree of suppression of type I collagen synthesis was a strong independent predictor of overall weight gain over the first 12 wk of life.
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PMID:Effects of dexamethasone treatment on bone and collagen turnover in preterm infants with chronic lung disease. 1092 89

Glucocorticoids, predominantly dexamethasone (DEX), are widely used to reduce the risk of prematurity-related chronic lung disease. However, prenatal DEX treatment links to adverse effects in later life, including hypertension. Given that sex differences exist in the blood pressure (BP) control, and that renal transcriptome is sex-specific, thus we intended to elucidate whether prenatal DEX-induced programmed hypertension is in a sex-specific manner and identify candidate genes and pathways using the whole-genome RNA next-generation sequencing (NGS) approach. Offspring were assigned to 4 groups (n=7-8/group): male control (MC), female control (FC), male DEX (MD), and female DEX (FD). Dexamethasone (0.1mg/kg body weight) or vehicle was intraperitoneally administered to pregnant SD rats from gestational day 16-22, to construct a DEX model. Rats were killed at 16weeks of age. Prenatal DEX induced sex-specific increase in BPs in male but not female adult offspring. Prenatal DEX elicited renal programming in a sex-specific fashion as demonstrated by 8 and 18 DEGs in male and female offspring, respectively. Among them, two genes, Hbb and Hba-a2, were shared. The resistance of female offspring to prenatal DEX-induced programmed hypertension is related to a lower Agt expression. Prenatal DEX induced programmed hypertension in adult male but not female offspring, which was related to renal programming affecting sex-biased genes and the RAS. Early identification of sex-specific underlying mechanisms could provide novel deprogramming strategy to reach maximal optimization in both sexes.
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PMID:Sex differences in renal transcriptome and programmed hypertension in offspring exposed to prenatal dexamethasone. 2752 2