Biomedical subjects

Tamerou Asrat

Publications and source records attributed to Tamerou Asrat.

7 recordsLinked to original sources

PubMed2006

Vaginal versus oral indomethacin in a rabbit model for non-infection-mediated preterm birth: an alternate tocolytic approach.

OBJECTIVE: We examined the hypotheses that vaginal indomethacin is more effective for prolonging gestation, and mediates its tocolytic actions via changes in cervical matrix metalloproteinase (MMP) activity, compared to oral. STUDY DESIGN: Pregnant rabbits induced with mifepristone received oral or vaginal indomethacin; or oral or vaginal vehicle once daily for 2 days. Premature delivery, fetal ductus arteriosus, and cervical MMP activity were assessed. RESULTS: Vaginal indomethacin delayed delivery >72 hours in 100% of the rabbits, extending gestation to 28.2 +/- 0.5 (P < .01) versus 26.4 +/- 0.3, 25.8 +/- 0.5, and 26.5 +/- 0.3 days, for vaginal placebo, oral indomethacin, and oral vehicle, respectively. Fetal ductus arteriosus was patent in all groups. Vaginal indomethacin decreased MMP-1, -8, and -9 activities and increased TIMP-1 levels in the cervix. CONCLUSION: Vaginal indomethacin is more effective than oral for prolonging gestation in the rabbit. Its tocolytic effects may be mediated, in part, by alterations in cervical MMP activity.

Administration, Intravaginal↗

PubMed2005

Effect of maternal administration of selective cyclooxygenase (COX)-2 inhibitors on renal size, growth factors, proteinases, and COX-2 secretion in the fetal rabbit.

BACKGROUND: Selective cyclooxygenase (COX)-2 inhibitors are currently being considered for management of preterm labor. COX-2 is an important regulator of fetal renal growth and function. Its inhibition may lead to congenital oligonephropathy. OBJECTIVES: We investigated whether maternal administration of a selective COX-2 inhibitor would adversely affect fetal renal growth. METHODS: Three groups of timed pregnant rabbits at 13 days gestation were examined. Group 1 received oral celecoxib (30 mg/kg/day) from 13 to 20 days gestation (Cel-A); group 2 received celecoxib from 13 to 28 days gestation (Cel-B), and group 3 received equivalent volumes of the vehicle from 13 to 28 days gestation. The fetuses were delivered by cesarean section at 29 days gestation. The kidneys were weighed and analyzed for vascular endothelial growth factor (VEGF) and its soluble receptors, matrix metalloproteinase (MMP)-2 and -9, tissue inhibitor of metalloproteinase (TIMP)-1 and -2, COX-2, and total cellular protein levels. Sections from the cortex and medulla were assessed histologically. RESULTS: Fetal kidney size was unaffected. VEGF levels were elevated in the Cel-B group. Soluble VEGF receptors, MMP-2, TIMP-1 and COX-2 levels remained unchanged. MMP-9 levels were suppressed in both treated groups, which resulted in significantly lower MMP-9/TIMP-1 ratios. Although TIMP-2 secretion was enhanced in the Cel-B group, MMP-2/TIMP-2 ratios were unaffected. No significant histological changes were detected. CONCLUSIONS: We conclude that maternal administration of therapeutic doses of celecoxib does not adversely affect fetal renal growth. MMP-9 is increased in various nephropathies, but may also have protective effects therefore its suppression by COX-2 inhibitors needs further study.

Animals↗

PubMed2005

Dose response of RU486 in a novel rabbit model of noninfectious preterm birth: comparative efficacy of 3 routes of administration.

OBJECTIVE: The purpose of this study was to examine whether the pregnant rabbit model can be used as a viable model for the study of non-infection-mediated preterm birth. STUDY DESIGN: Timed pregnant New Zealand rabbits were injected with a single dose of RU486 on day 22 of gestation. Three doses (50 mg, 75 mg, and 100 mg) were administered intramuscularly, intraperitoneally, or subcutaneously. The rabbits were monitored for preterm delivery. Progesterone, cortisol, and cytokine levels were examined before the induction and after delivery. Uterine and cervical progesterone, cortisol, and cytokine levels were determined after delivery. RESULTS: RU486 resulted in 100% preterm delivery in all doses and modes of administration, compared with 0% of controls. Intramuscular administration appeared to generate the most favorable preterm delivery time. Rabbits that received 100 mg RU486 intramuscularly showed significantly decreased serum progesterone levels and uterine progesterone levels, compared with 100 mg subcutaneously and intraperitoneally. CONCLUSION: RU486 that was administered intramuscularly appears to be a potent and effective method for inducing preterm birth. This model of hormonally mediated preterm birth might serve as a useful model for the investigation of the possible mechanisms of preterm labor.

Abortifacient Agents, Steroidal↗

PubMed2003

Effect of the antenatal administration of celecoxib during the second and third trimesters of pregnancy on prostaglandin, cytokine, and nitric oxide levels in rabbits.

OBJECTIVE: The purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13 to 28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Blood and tissue were assayed for prostaglandin, cytokine, and nitric oxide oxidation products. RESULTS: Preterm delivery occurred in 4 of 11 controls, 0 of 9 in celecoxib-A, and 0 of 8 in celecoxib-B. Plasma prostaglandin F(2alpha) was reduced in both treated groups at 20 days and at delivery in celecoxib-B. Plasma thromboxane B(2) was suppressed in celecoxib-B at 20 days and delivery. Cervical prostaglandin E(2) was increased; uterine and cervical plasma thromboxane B(2) declined in celecoxib-B. Celecoxib administration suppressed plasma nitric oxide oxidation products at delivery and cervical nitric oxide oxidation products in celecoxib-B. Uterine and cervical interleukin-1beta and interleukin-6 were decreased, and uterine tumor necrosis factor-alpha increased in celecoxib-B. CONCLUSION: Further studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.

Animals↗

PubMed2003

Response of fetal prostanoids, nitric oxide, and ductus arteriosus to the short- and long-term antenatal administration of celecoxib, a selective cyclo-oxygenase-2 inhibitor, in the pregnant rabbit.

OBJECTIVE: The purpose of this study was to test the hypothesis that the maternal administration of therapeutic doses of celecoxib would not affect ductus arteriosus patency or alter renal and hepatic prostanoids in the fetal rabbit. STUDY DESIGN: Pregnant rabbits received celecoxib from 13 to 20 days (celecoxib-A), from 13-28 days (celecoxib-B), or vehicle from 13 to 28 days by gavage. Fetal serum and lung tissue were analyzed for nitric oxide oxidation products. Fetal plasma, liver, and kidney were analyzed for prostaglandin levels. RESULTS: The ductus arteriosus was patent in both treatment groups. Celecoxib induced elevations of plasma prostaglandin E(2) production. In celecoxib-B liver and kidney, the 6-keto-prostaglandin F(1alpha) and prostaglandin F(2alpha) levels were increased, and the prostaglandin E(2) and thromboxane B(2) levels were decreased substantially. CONCLUSION: This preliminary evaluation demonstrates that the maternal administration of celecoxib does not influence fetal ductus arteriosus patency adversely in rabbits.

Analysis of Variance↗

PubMed2003

Antenatal administration of celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, appears to improve placental perfusion in the pregnant rabbit.

To investigate the effects of celecoxib on fetal growth, and placental prostanoid and nitric oxide (NO) production in fetal rabbits, pregnant rabbits received celecoxib (30 mg/kg per day) from 13 to 20 days (Cel-A), from 13 to 28 days (Cel-B), or vehicle from 13 to 28 days gestation. Fetal body and organ weights, and measurements of linear growth were recorded. The placentas were weighed and analyzed for prostaglandins (PGs), NO oxidation products (NOx), and total cellular protein levels. Placental prostaglandin E2 (PGE2) and NOx levels increased (P < or = 0.05), while thromboxane B2 levels were suppressed (P < or = 0.01) in Cel-B group. Tail length and brain weight were greater, while lung weights were lower in the Cel-B group (P < or = 0.05). Maternal administration of celecoxib appears to preferentially increase placental vasodilators and decrease placental TxA2, suggesting that the drug may increase uteroplacental perfusion without adverse fetal outcome.

6-Ketoprostaglandin F1 alpha↗

PubMed2003

Placenta previa: does its type affect pregnancy outcome?

Our objective was to compare pregnancy outcomes associated with different types of placenta previa. This is a retrospective analysis of pregnancies complicated by placenta previa, from January 1990 to December 1997. Descriptive statistics and comparison analyses were performed. One hundred seventy-five singleton pregnancies beyond 24 weeks that were complicated by complete, partial, or marginal previa were included. Differences in pregnancy outcomes between complete, partial, and marginal previas were: onset of bleeding (29.9 +/- 4.5 versus 32.5 +/- 6.9 versus 32.7 +/- 5.0 weeks, respectively, p < 0.05), antepartum hospitalization (60.7% versus 38.1% versus 35.1%, respectively, p < 0.05), gestation at delivery (34.7 +/- 3.1 versus 37.4 +/- 2.6 versus 36.1 +/- 3.0 weeks, respectively, p < 0.05), birth weight (2498.3 +/- 746.8 versus 2978.8 +/- 568.3 versus 2813.4 +/- 728.4 g, respectively, p < 0.05), and hysterectomy at time of cesarean delivery (20.5% versus 0% versus 8.1%, respectively, p < 0.05). For all outcome parameters, the partial and marginal previa groups did not differ. Women with complete placenta previa, as diagnosed with modern ultrasound techniques, had poorer pregnancy outcome. They were more likely to deliver prematurely and were more likely to require a hysterectomy at the time of cesarean delivery.

Adult↗