Delay of preterm delivery in sheep by omega-3 long-chain polyunsaturates.
A positive correlation has been shown between dietary intake of long-chain omega-3 fatty acids in late pregnancy and gestation length in pregnant women and experimental animals. To determine whether omega-3 fatty acids have an effect on preterm labor in sheep, a fish oil concentrate emulsion was continuously infused to six pregnant ewes from 124 days gestational age. At 125 days, betamethasone was administered to the fetus to produce preterm labor. Both the onset of labor and the time of delivery were delayed by the fish oil emulsion. Two of the omega-3-infused ewes reverted from contractions to nonlabor, an effect never previously observed for experimental glucocorticoid-induced preterm labor in sheep. Maternal plasma estradiol and maternal and fetal prostaglandin E2 rose in control ewes but not in those infused with omega-3 fatty acid. The ability of omega-3 fatty acids to delay premature delivery in sheep indicates their possible use as tocolytics in humans. Premature labor is the major cause of neonatal death and long-term disability, and these studies present information that may lead to a novel therapeutic regimen for the prevention of preterm delivery in human pregnancy. (+info)
Secondary glioblastoma remarkably reduced by steroid administration after anaplastic transformation from gliomatosis cerebri--case report.
A 45-year-old female presented with gliomatosis cerebri manifesting as hemiballismus-like involuntary movement in the arm, motor weakness in the leg, and hypesthesia in her left side. Computed tomography showed only diffuse swelling of the right cerebral hemisphere, but T2-weighted magnetic resonance imaging revealed a diffuse lesion spreading from the right thalamus to the temporal, parietal, and occipital lobes on the same side. No abnormal enhancement was recognized. Cerebral angiography showed no specific finding. A right occipital lobectomy was performed to confirm the diagnosis of gliomatosis cerebri. Anaplastic transformation was recognized 5 months later. The disease did not resolve with radiation or interferon administration, but steroid therapy achieved remarkably effective tumor regression. The patient died due to pneumonia. Autopsy showed the features of diffuse glioblastoma. Steroid therapy may be an effective treatment for gliomatosis cerebri before the terminal stage. (+info)
Betamethasone-mediated vascular dysfunction and changes in hematological profile in the ovine fetus.
Glucocorticoid administration to fetal sheep induces a sustained systemic blood pressure rise and an associated increase in femoral vascular resistance. We utilized a small vessel myograph to compare isometric vascular responses of small femoral arterial branches from fetal sheep infused intravenously with either betamethasone or vehicle in vivo from 128 days gestation. Changes in hematological parameters were also determined. Betamethasone was infused for 48 h to produce fetal plasma betamethasone concentrations similar to those observed in human fetuses after maternal treatment with betamethasone to accelerate fetal lung maturation. When compared with vessels removed from vehicle-infused fetuses, vessels obtained from betamethasone-treated fetuses exhibited 1) enhanced sensitivity to depolarizing potassium solutions; 2) no differences in response to the thromboxane mimetic U-46619 or norepinephrine; and 3) differential responses to vasodilators, enhanced sensitivity to ACh, but decreased response to bradykinin and forskolin. In addition, erythrocyte and leukocyte counts were increased in betamethasone-infused fetuses. These observations indicate that multiple mechanisms operate to increase fetal vascular resistance during antenatal betamethasone exposure. (+info)
Concentration of steroids in bovine peripheral plasma during the oestrous cycle and the effect of betamethasone treatment.
Testosterone, oestradiol and progesterone were measured in peripheral plasma during the oestrous cycle of 6 heifers. Oestradiol and progesterone results confirmed earlier reports. Concentration of testosterone on the day of oestrus was 40+/-3 pg/ml (mean+/-S.E.M.), and two peaks were detected during the cycle, one 7 days before oestrus (1809+/-603 pg/ml) and the other (78+/- 7 pg/ml) on the day before the onset of oestrus. The concentration of progesterone declined in most cases 1 day after the maximum concentration of testosterone. Betamethasone treatment in 5 heifers extended luteal function by an average of 10 days: plasma androstenedione and oestradiol concentrations were unaltered; cortisol values were depressed for at least 16 days after treatment; testosterone concentrations were lowered by 13+/-2-4% during treatment, and except in one heifer the peak on Day -7 was abolished. (+info)
Functional capacity of fetal zone cells of the baboon fetal adrenal gland: a major source of alpha-inhibin.
We have shown that ACTH receptor mRNA expression and steroidogenesis were increased in the transitional zone and decreased in the fetal zone of the baboon fetal adrenal in the second half of gestation. Thus, we proposed that there is a divergence in ACTH receptor-mediated zone-specific steroidogenesis within the fetal adrenal during mid to late gestation. We have also demonstrated that fetal serum alpha-inhibin levels decline with advancing development. It is possible, therefore, that the alpha subunit of inhibin provides a good marker of fetal zone cellular function and that the changes in circulating fetal alpha-inhibin with advancing pregnancy reflect ontogenetic changes in fetal adrenal cortical zone-specific cell function. However, it remains to be determined whether the fetal adrenal is a major source of circulating alpha-inhibin in the fetus and whether alpha-inhibin is expressed in the fetal, definitive, and/or transitional zones. Therefore, the current study compared fetal serum alpha-inhibin levels with immunocytochemical localization of alpha-inhibin in baboon fetal adrenals obtained on Days 60 (early), 100 (mid), and 165 or 182 (late) of gestation (term averages Day 184) from animals untreated or treated with betamethasone, which we previously demonstrated suppressed fetal pituitary ACTH and adrenal weight. Fetal serum alpha-inhibin levels (mean +/- SE) were greater (p < 0.05) at mid (5863 +/- 730 microliter eq/ml) than at late (3246 +/- 379) gestation and were reduced (p < 0. 05) by betamethasone. The inhibin alpha subunit was expressed in abundant quantities in the fetal adrenal cortex, but not in medulla, throughout gestation. At mid and late gestation, alpha-inhibin was expressed throughout the fetal adrenal cortex but most intensely in the innermost area of fetal zone cells. By late gestation, the fetal adrenal exhibited a gradient of alpha-inhibin expression. Thus, the outermost definitive zone cells were devoid of alpha-inhibin, the transitional zone exhibited a relatively low alpha-inhibin content, and fetal zone cells continued to exhibit extensive expression of alpha-inhibin. Betamethasone diminished the intensity of alpha-inhibin expression throughout the fetal adrenal cortex. These results indicate that the fetal adrenal fetal zone is a significant source of circulating alpha-inhibin in the baboon fetus and that alpha-inhibin provides a good marker to study the developmental regulation of fetal zone-specific adrenocortical function. (+info)
Spontaneous labour at term is associated with fetal monocyte activation.
The aetiology of both term and preterm labour remains incompletely understood. Maternal infectious diseases as well as intra-uterine infections were shown to be a well established cause of uncontrollable preterm delivery, indicating that inflammatory reactions, regulated by maternal immunecompetent cells, are implicated in labour-promoting mechanisms. To investigate the possibility that the activation of the fetal immune system may be involved in labour induction, we examined cytokine production patterns of different cord blood cell populations obtained from neonates after spontaneous onset of normal term labour and vaginal delivery (n = 25), vaginal delivery but induced term labour (n = 17), and preterm delivery because of uncontrollable labour (n = 27, 20 patients received corticoid treatment for fetal lung maturation), in comparison with cells obtained from neonates after elective term caesarean delivery in the absence of labour (n = 15). Our results demonstrate that spontaneous term labour, but not induced term labour, was associated with significantly increased IL-6 production by myelomonocytic cell populations. Preterm delivery due to uncontrollable labour with resistance to tocolysis was not associated with increased IL-6 production by fetal myelomonocytic cells. Two-colour flow cytometry combined with intracellular cytokine staining was used to identify fetal monocytes as sources of labour-associated IL-6 release at term. We did not find any activation of cord blood T cells in association with spontaneous term or uncontrollable preterm labour. Therefore, fetal T cell responses may not cause monocyte activation. Our results suggest that increased release of IL-6 from fetal monocytes is involved in mechanisms promoting normal term, but not preterm labour, and that mechanisms inducing term and preterm labour are completely different. (+info)
Developmental expression of and effect of betamethasone on the messenger ribonucleic acid levels for peptide growth factors in the baboon fetal adrenal gland.
In the present study, we determined whether expression of the messenger ribonucleic acids (mRNAs) for insulin-like growth factor-II (IGF-II), and its principal IGF type-1 receptor and IGF-binding protein-2 (IGFBP-2), as well as basic fibroblast growth factor (bFGF), was developmentally regulated in the baboon fetal adrenal gland. In the second phase of this study, fetal pituitary ACTH was suppressed by the administration of betamethasone to determine the possible effect on the mRNA levels for those factors, i.e. IGF-II and IGFBP-2, shown to be expressed at high levels in the adrenal late in fetal development. Adrenals were obtained from fetuses delivered via Cesarean section on days 60 (early), 100 (mid), and 165 (late) of gestation (term=184 days) from untreated baboons and on day 165 from baboons in which betamethasone was administered to the fetus, or to fetus and mother, every other day between days 150 and 164 of gestation. Although the mRNA levels of IGF-II in the fetal adrenal were similar at early, mid and late gestation, IGF type-1 receptor mRNA levels were approximately 2- to 3-fold greater (P<0.01) at mid than at early or late gestation. In contrast, there was an increase (P<0.001) in fetal adrenal IGFBP-2 and bFGF mRNA levels in late gestation. Although fetal adrenal weights and width of the zone of definitive/transitional cells exhibiting immunocytochemical staining for Delta(5)-3beta-hydroxysteroid dehydrogenase (3beta-HSD) were markedly suppressed (P<0.01) by the administration of betamethasone, IGF-II and IGFBP-2 mRNA expression was not decreased. In summary, very different patterns of mRNA levels for IGF-II, IGF type-1 receptor, IGFBP-2 and bFGF were exhibited in the developing baboon fetal adrenal gland, which may reflect functionally important differences in their respective cellular localization within the cortex, as well as a divergence in the functional development of the fetal, transitional and definitive zones of the baboon fetal adrenal cortex. (+info)
Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.
BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants. (+info)