Diprolene
Effect of prenatal glucocorticoid on fetal lung ultrastructural maturation in hyt/hyt mice with primary hypothyroidism.

Ansari MA, de Mello DE, Devaskar UP.

Department of Pediatrics, Saint Louis University School of Medicine and the Pediatric Research Institute, MO, USA.

Glucocorticoids (GC) and thyroid hormones (TH) accelerate fetal lung maturation. Though GC are used clinically, the mechanisms of GC-induced fetal lung maturity remain unclear. Prenatal GC increase fetal TH activity in humans and in animals. Thus, it is possible that increased fetal TH activity after prenatal GC plays a role in accelerating fetal lung maturation. However, this hypothesis has remained untested due to the lack of a suitable animal model. In the hyt/hyt mouse primary hypothyroidism occurs due to a point mutation in the beta subunit of the thyroid-stimulating hormone receptor of the thyroid gland, and it is transmitted in an autosomal recessive manner. We studied the effect of maternal betamethasone on fetal lung ultrastructure in hyt/hyt (hypothyroid) and Balb-c (euthyroid) mice. Hypothyroid mice were made euthyroid by T3 supplementation and mated to carry hypothyroid pups. Vehicle (n = 6) or betamethasone (n = 6) was injected intraperitoneally twice daily into the doe on days 16 and 17 of gestation. Fetal lungs on 18 days of gestation were subjected to ultrastructural morphometric analysis. The number of lamellar bodies per type II cell increased after betamethasone in Balb-c (2.10+/-0.31 vs. 3.43+/-0.37) and hyt/hyt (0.77+/-0.28 vs. 3.85+/-0.26) mice. The alveolar-to-parenchymal ratio was less in the vehicle-treated hyt/hyt (0.082+/-0.024) as compared with the vehicle-treated Balb-c (0.30+/-0.05) mice, while prenatal betamethasone increased the alveolar-to-parenchymal ratio in the hyt/hyt (0.227+/-0.034) but not in the Balb-c (0.26+/-0.04) mice. The glycogen-to-nucleus ratio was higher in betamethasone-treated hyt/hyt mice (1.46+/-0.20) when compared to vehicle-treated hyt/hyt (0.89+/-0.14) or Balb-c (1.01+/-0.17) or betamethasone-treated Balb-c (0.81+/-0.13) mice. Though tubular myelin was readily apparent in the airspace lumen of betamethasone-treated Balb-c mice, it was absent in betamethasone-treated hyt/hyt fetal lungs. We conclude that fetal thyroid plays an important role in accelerating some aspects of fetal lung ultrastructural maturation from GC stimulation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10658828&dopt=Abstract betamethasone Diprolene AF



Diprolene
Effect of anti-inflammatory agents on corneal wound-healing process after surface excimer laser keratectomy.

Kaji Y, Amano S, Oshika T, Obata H, Ohashi T, Sakai H, Shirasawa E, Tsuru T, Yamashita H.

Department of Ophthalmology, University of Tokyo Faculty of Medicine, Tokyo, Japan.

PURPOSE: To investigate the effect of anti-inflammatory agents on conjunctival inflammation and corneal haze formation after excimer laser keratectomy. SETTING: Department of Ophthalmology, University of Tokyo Faculty of Medicine, Tokyo, Japan. METHODS: After excimer laser keratectomy was performed in 21 rabbits (42 eyes), saline, betamethasone 0.1%, or diclofenac 0.1% was topically applied 6 times a day for 4 weeks and then 3 times a day for 8 weeks. The degree of conjunctival inflammation was determined 1, 2, 3, and 7 days after the keratectomy. The degree of corneal haze was quantitatively measured using a digital analyzer before and once a week after the keratectomy. The expression of type IV collagen in the corneas at baseline and 4 and 12 weeks after the keratectomy was examined immunohistochemically. RESULTS: Compared with saline, betamethasone and diclofenac significantly decreased early-phase conjunctival inflammation. Betamethasone significantly inhibited corneal haze formation compared with saline at 3 to 5 and 8 to 12 weeks. Diclofenac did not inhibit corneal haze formation significantly. Although betamethasone tended to be more effective in inhibiting corneal haze formation and deposition of type IV collagen than diclofenac, there was no statistical difference between the 2 anti-inflammatory agents. CONCLUSION: Topically applied betamethasone effectively suppressed corneal haze formation after excimer laser keratectomy. Diclofenac was not statistically effective in inhibiting corneal haze formation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10713241&dopt=Abstract betamethasone Diprolene AF



Diprolene
Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term.

Sloboda DM, Newnham JP, Challis JR.

Departments of Physiology and Obstetrics and Gynecology, University of Toronto, Toronto M5S 1A8, Canada. d.sloboda utoronto.ca

Synthetic glucocorticoids have become an important clinical tool with which to advance fetal lung maturation in women at risk of early preterm birth, and this has succeeded in reducing neonatal mortality and morbidity from respiratory distress syndrome. Although previous studies have shown that glucocorticoids have deleterious consequences on fetal development, there is little information regarding the effects of clinically relevant repeated maternal doses of glucocorticoids on fetal growth and hypothalamic-pituitary-adrenal (HPA) function. We hypothesised that repeated prenatal exposure to increased concentrations of glucocorticoids would alter fetal growth and HPA axis development. Pregnant ewes were injected with betamethasone (0.5 mg/kg) or vehicle at 104, 111 and 118 days of gestation (term 150 days). Animals were sacrificed at 125 and 146 days of gestation, at which time fetal weights were recorded. Maternal and fetal blood samples were gathered and fetal tissue collected. Maternal oestradiol concentrations were significantly greater than those in controls at 125 days of gestation, but were not different at 146 days. Maternal plasma progesterone concentrations were similar between groups at both 125 and 146 days of gestation. Weight at birth was significantly reduced by 23% at 125 days and 19% at 146 days of gestation (P<0.05) after exposure to glucocorticoid. Cord plasma ACTH concentrations were not significantly different between groups at day 125, but were significantly increased in day 146 fetuses of ewes that had received betamethasone (P<0.05). Cord plasma cortisol concentrations followed the same trend, although differences were not statistically significant. Cord plasma corticosteroid binding capacity (CBC) was significantly increased at 125 days of gestation in fetuses of betamethasone-treated animals (P<0.05), but not at 146 days of gestation. To examine the mechanisms regulating the increase in cord plasma ACTH of 146-day fetuses, we used in situ hybridisation to determine the distribution and levels of mRNA encoding key pituitary and hypothalamic neuropeptides of the HPA axis. In pituitaries of 146-day fetuses, there were no significant differences in the regional pattern of distribution or amounts of pro-opiomelanocortin (POMC) mRNA between betamethasone-treated animals and controls, in either the pars intermedia or the inferior and superior regions of the pars distalis. Neither prohormone convertase (PC)-1 nor PC-2 mRNA levels in pituitaries of 146-day fetuses were significantly different between treatment groups. After maternal betamethasone, immunoreactive ACTH peptide content in the fetal pars distalis was not different but glucocorticoid receptor (GR) mRNA levels in the pars distalis were increased significantly (P<0.05). No significant difference in distribution pattern or concentrations of corticotrophin-releasing hormone (CRH) mRNA, GR mRNA, oxytocin mRNA and pre-proenkephalin mRNA were found in hypothalami from fetuses at 146 days of gestation after betamethasone treatment. We conclude that antenatal betamethasone given to pregnant sheep in a manner similar to that used in human obstetric practice results in reduced weight at birth at 125 and 146 days, and altered basal cord levels of plasma ACTH and corticosteroid binding capacity, but these changes are not reflective of changes in steady state concentrations of POMC and CRH mRNA in the fetal pituitary or hypothalamus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10750038&dopt=Abstract betamethasone Diprolene AF



Diprolene
The effect of betamethasone on salivary estriol.

Leff RP, Goldkrand JW.

Department of Obstetrics and Gynecology, Memorial Health University Medical Center, Savannah, Georgia 31403-3089, USA.

OBJECTIVE: Study of the degree and pattern of salivary estriol suppression after administration of betamethasone. STUDY DESIGN: A total of 26 patients with singleton pregnancies (> 24 but < 35 weeks' gestation) in preterm labor with intact membranes had salivary estriol collected prior to betamethasone administration and then daily in late afternoon to evening. All patients were receiving magnesium sulfate. Five patients received a second dose of steroids 1 week after the first. Specimens were frozen and later batch analyzed. RESULTS: Betamethasone induced a mean 35.1 +/- 18.2% decrease in salivary estriol which reached its nadir in 1-6 days. By day 6, the salivary estriol in all patients remained suppressed. A second dose of betamethasone caused a further decrease in estriol. CONCLUSION: Betamethasone suppressed salivary estriol in all patients, consistent with the effect of glucocorticoids on fetal adrenal estriol precursors. The suppression persisted for at least 1 week.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12380676&dopt=Abstract betamethasone Diprolene AF



Diprolene
Corticosteroids and fetal vasculature: effects of hydrocortisone, dexamethasone and betamethasone on human umbilical artery.

Potter SM, Dennedy MC, Morrison JJ.

OBJECTIVE: To investigate the direct effects of corticosteroids on human umbilical artery resistance, in vitro. DESIGN: Prospective laboratory study. SETTING: University teaching hospital. SAMPLES AND METHODS: Umbilical artery samples were obtained following normal, term deliveries (n = 50) and dissected rings were suspended for isometric recording under physiological conditions. The effects of hydrocortisone (10(-9) - 10(-4) M), dexamethasone (10(-9) - 10(-4) M) and betamethasone (10(-9) - 10(-4) M) on umbilical artery resistance were measured in vitro. MAIN OUTCOME MEASURES: Changes in umbilical artery resistance, in vitro. RESULTS: Hydrocortisone (n = 12) exerted a vasodilatory effect on human umbilical artery at all concentrations studied compared with vehicle control experiments (n = 12) (P < 0.0001). The mean net relaxant effect of hydrocortisone ranged from 11.77% (10(-9) M) to 57.01% (10(-4)). Both exogenous compounds, dexamethasone (n = 12) and betamethasone (n = 12), similarly exerted a significant relaxant effect on human umbilical artery tone (P < 0.05-0.01), compared with vehicle control experiments (n = 12). The mean net relaxant effect of dexamethasone ranged from 14.43% (10(-9) M) to 38.12% (10(-4)) and that of betamethasone ranged from 6.02% (10(-9) M) to 42.30% (10(-4)), in a cumulatively increasing fashion. There was a non-significant trend towards a greater vasodilatory effect of dexamethasone than betamethasone at lower bath concentrations studied. CONCLUSION: Corticosteroids exert a direct and potent vasodilatory effect on human umbilical artery resistance in vitro, thus providing an explanation for the previously unexplained vascular effects associated with antenatal administration of corticosteroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12387465&dopt=Abstract betamethasone Diprolene AF