Tamerou Asrat

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.

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

OBJECTIVEnThe purpose of this study was to examine the effects of celecoxib on prostaglandin, cytokine, and nitric oxide synthesis in the pregnant rabbit.nnnSTUDY DESIGNnPregnant 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.nnnRESULTSnPreterm 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.nnnCONCLUSIONnFurther studies are required to evaluate the therapeutic benefits of cyclo-oxygenase-2 inhibitors in the setting of preterm parturition.

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.

Meconium has no lecithin or sphingomyelin but affects the lecithin/sphingomyelin ratio.

OBJECTIVEnAlthough a few studies have evaluated the effect of meconium on the lecithin/sphingomyelin ratio for testing of fetal lung maturity, to date these studies have assessed only the lecithin-sphingomyelin ratio of amniotic fluid contaminated with meconium. The purpose of this study was (1) to determine whether meconium by itself has a lecithin/sphingomyelin ratio and, if so, (2) to determine whether the lecithin/sphingomyelin ratio is constant.nnnSTUDY DESIGNnA lecithin/sphingomyelin ratio was obtained by standard thin-layer chromatography on the first meconium stool of 20 neonates between 31 weeks and term. A quantitative assay was then performed on a sample from each gestational age (7 samples ranging from 31 weeks to term) to confirm the presence of lecithin and sphingomyelin.nnnRESULTSnThe 20 samples had atypical thin-layer chromatographic migratory patterns in the zones for lecithin and sphingomyelin. The presumed lecithin/sphingomyelin ratios ranged from 1.1 to 3.6, with no correlation with gestational age. However, the quantitative assay did not detect the presence of lecithin or sphingomyelin in any of the analyzed samples.nnnCONCLUSIONSnMeconium does not appear to contain lecithin or sphingomyelin but has an unidentified moiety whose migratory pattern, as shown by qualitative standard thin-layer chromatography, is similar to that of lecithin with sphingomyelin. Therefore the presence of meconium in amniotic fluid may falsely raise or lower the lecithin/sphingomyelin ratio and confuse fetal lung maturity interpretations.