Prostaglandins最新文献

This study was conducted to compare the levels of prostaglandin E2 (PGE₂) released by cultured granulosa cells collected from normally-ovulating women (normal cells, NC) and those with polycystic ovaries (polycystic ovary granulosa cells, POGC). Granulosa cells were collected from 7 normal women and 7 anovulatory women with polycystic ovaries. Both groups underwent laparoscopic oocyte retrieval for gamete intra-fallopian transfer. Cell cultures were carried out under basal conditions and in the presence of various substances known to influence PGE2 biosynthesis. Prostaglandin E2 concentrations in the incubation media were taken as a marker of cyclo-oxygenase activity.

Unexpectedly, POGC appeared to release greater amounts of PGE2 compared to the NC. There was no difference between the levels of PGE2 produced by the two types of cells during the first 3 hours after cell explants, whereas a difference (P<0.01) was observed after 24 and 48 hours of incubation. Interleukin-1β enhanced PGE2 secretion (P<0.01) in both POGC and NC, while lipopolysaccharide increased prostaglandin release only by the NC cells. Indomethacin inhibited PGE2 production to a greater extent in POGC (from −70 to −90% with respect to basal release, P<0.01) than NC (approximately −50%, P<0.01). Blockade by indomethacin and the weak inhibitory effect of the glucocorticoid, dexamethasone (P<0.05 only in NC, and only at 24 hours), provided pharmacological evidence that PG production by granulosa cells in vitro might depend primarily on constitutive cyclo-oxygenase activity.

Objective: To determine if prostaglandin (PG) E₂ cervical ripening is safe and effective in high-risk preterm pregnant women who do not have an indication for immediate delivery.

Methods: This was a retrospective case-control study of preterm pregnant women treated with sequential PGE2 gel between 3/1/92 and 3/1/95. Study subjects were between 24 and 36 weeks gestation, had intact membranes, and complications requiring inpatient monitoring but not immediate delivery. PGE₂ gel was inserted serially until either maternal or fetal deterioration required intervention, fetal maturity was achieved, a Bishop ≥ 7 was reached, or the patient improved and was discharged. Control subjects were matched for inclusion criteria and diagnoses on admission.

Results: A total of 22 study and 22 control patients were evaluated. The gestational age at admission was 32.3 ± 2.8 versus 31.8 ± 2.9 weeks. The mean number of PGE₂ gel applications was 11.6 over a mean of 5.0 days. Intervention during ripening was required in 11 (50%). A Bishop score ≥ 7 without labor was achieved in 11 (50%), and labor during the ripening process occurred in 2 (9%). The mean time from Bishop ≥ 7 to delivery was 2.6 days. The total cesarean delivery rate was 10 (45%) versus 15 (68%), in the control group (P = NS). Neonatal outcomes were similar.

Conclusions: Sequential PGE₂ gel cervical ripening when used in preterm pregnant women improves the Bishop score, and has a low incidence of spontaneous preterm labor.

The effects of misoprostol, a prostaglandin E1 analog, and prostaglandin E2 on proteoglycan biosynthesis and loss were studied in unloaded and mechanically loaded mature bovine articular cartilage explants. The prostaglandins were administered daily at dosages of 0, 10, 100 and 1000 ηg/ml for up to seven days, and proteoglycan biosynthesis determined by measurement of radiolabelled sulfate incorporation. The presence of misoprostol lead to a significant (p<0.001) dose-dependent inhibition (30%–50%) in proteoglycan biosynthesis which was also dependent on exposure time (p<0.05). A significant decrease in biosynthesis (34%) was also found for prostaglandin E2, but only at the highest dose (1000 ηg/ml). Proteoglycan catabolism rates were not affected by either substance as assessed by loss of newly synthesized proteoglycan. The application of a continuous cyclic mechanical compressive load (stress of 1.0 MPa at 1 hertz for 24 hours) resulted in a significant inhibition of proteoglycan biosynthesis (up to 50%) as compared to unloaded explants. However, there was no additive effect when mechanical load and misoprostol or prostaglandin E2 were combined. These results suggest that prostaglandins may have a role in the degenerative and repair process in various forms of arthritis where elevated intra-articular levels of prostaglandin E2 are present.

Previous reports revealed that interleukin-1(IL-1) was involved in the process of premature labor in the cases with intrauterine infection. However, the roles of the cytokine in normal spontaneous labor remain uncertain. The present studies aimed at determining the involvement of the cytokine in prostaglandin (PG)E₂ production during labor by the third trimester decidual cells. The cells were obtained at the time of normal spontaneous delivery (NVD) and elective cesarean section (ECS). The NVD cells produced significantly more amount of PGE2 than the ECS cells and the both cells responded to the addition of IL-1β to increase PGE₂ production. A specific inhibitor of cyclooxygenase-2 (COX-2), NS398, decreased basal PGE2 production and inhibited the stimulatory effect of IL-1f in a dose dependent manner in NVD cells. The NVD cells secreted more amount of IL-1 fl than the ECS cells and contained more amount of preprocessed 31kD IL-1 fl inside the cells. The addition of recombinant soluble human IL-1 receptor (type I) not only blocked the effect of IL-1β on PG secretion, but significantly reduced the basal production of PGE2 by NVD cells. These results indicate that decidual PG production depends upon COX-2 after the onset of labor. Besides it seems likely that endogenously produced IL-1β may be involved in autocrine fashion in inducing COX-2 after the onset of labor.

Ovulation, oocyte maturation and PGE and PGF_2α production by oocyte-cumulus complexes were evaluated in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin. Diabetic rats had normal estrous cycles, but ovulated a lower number of oocytes at estrus. When oocytes from control and diabetic rats obtained at proestrus were matured “in vitro” during 1, 2 or 4 hours (hr) of culture, differences were not found in the percent of germinal vesicle breakdown between both experimental groups. PGE and PGF_2α accumulation was higher in ovulated oocyte-cumulus complexes when compared to immature or “in vitro”-matured oocyte-cumulus complexes in both normal and diabetic rats. When control and diabetic rats are compared, more PGE and PGF_2α accumulation was observed in immature, “in vitro”-matured and in ovulated oocytecumulus complexes.

A lower number of oocytes ovulated and increased oocyte-cumulus complexes prostaglandin production has been observed in this mildly diabetic experimental model. These abnormalities are similar to those previously found when 10 day embryos were evaluated in noninsulin-dependent diabetic rats.

Δ¹²-prostaglandin J₂ (PGJ₂) is a dehydration product of PGD₂ and thought to be the most potent antitumor agent among prostaglandin compounds. We examine the cytotoxic effects of PGJ₂ on the cell growth of leukemia/lymphoma cells. PGJ₂ inhibited the growth of both human PL-21 myeloid leukemia and RC-K8 pre-B lymphoma cells in culture in a dose-dependent manner with fragmentation of nucleus and formation of apoptotic body. Agarose gel electrophoresis revealed DNA ladder formation in the cells treated with PGD₂. Furthermore, PGJ₂ induced a rapid and transient expression of apoptosis-related protooncogene, c-fos, in both cells. The gene transcriptional rate was remarkably increased approximately 3.3-fold in PGJ₂ treated cells, but the stability of c-fos mRNA was not significantly changed. Inhibition of de novo protein synthesis with cycloheximide increased c-fos mRNA stability but not abrogated PGJ₂-induced c-fos transcription. These data suggest that PGJ₂ can induce apoptosis of human leukemia/lymphoma cells and the rapid activation of c-fos protooncogene transcription in which de novo protein synthesis is not required.

The effects of prostaglandin E₂ (PGE₂) on platelet cyclic AMP formation were examined and compared with effects on cloned prostaglandin receptors. PGE₂ gave a weak stimulation of adenyl cyclase in platelets compared with the PGI₂ analog Iloprost. In the presence of the adenyl cyclase stimulator forskolin, the response to PGE₂ was amplified in a synergistic manner. By contrast, in the presence of Iloprost, PGE₂ inhibited cyclic AMP formation. We postulate that the weak platelet response to PGE₂ is due to co-localization of a PGE₂ receptor that couples to stimulation of adenyl cyclase with the EP3 prostaglandin receptor that binds PGE₂ tightly and inhibits adenyl cyclase. In support of this postulate, we compared the responses obtained with platelets with those of cloned EN (stimulatory) and EP3 (inhibitory) prostaglandin receptor subtypes and show similar dose-response curves for stimulation and inhibition of cyclic AMP formation between platelets and cloned receptors.

The modulation of the production of prostacyclin and thromboxane from rat and cat aortic tissue slices by different vasoactive agents has been studied in order to reveal whether the release of these main two vasoactive prostanoids goes in parallel or may be controlled independently. Norepinephrine, isoproterenol, phentolamine, propranolol, angiotensin II, vasopressin, bradykinin, thrombin, verapamil, gallopamil, dopamine or methionin enkephalin were added to the incubation medium and 6-keto-PGF_1α (the stable metabolite of prostacyclin) and TXB₂ (the stable metabolite of thromboxane) were determined in the supernatant by radioimmunoassay. The ratio of the release of prostacyclin and thromboxane was computed. Norepinephrine increased both prostacyclin and thromboxane release. Isoproterenol increased the ratio of prostacyclin and thromboxane released in cat aortic tissue slices. Phentolamine and propranolol had no effects. Angiotensin II induced a slight but statistically insignificant increase in the ratio of the two prostanoids released. Vasopressin increased thromboxane release only. Bradykinin stimulated the prostacyclin while thrombin stimulated the thromboxane release. Verapamil decreased both prostacyclin and thromboxane production. Gallopamil decreased prostacyclin release and increased thromboxane release from vessel wall slices in a certain concentration range causing a characteristic dose dependent minimum in the ratio of prostacyclin and thromboxane release. Dopamine separately increased prostacyclin release while enkephalin had no significant effect. The data obtained show that in vascular tissue some unidentified yet cytophysiological mechanisms might exist which specifically control the activities of the prostacyclin synthase and thromboxane synthase enzymes.

Lipid mediators released by inflammatory and immune cells play an important role in inflammatory and immune processes. Most attention has been focussed on arachidonic-derived mediators, including prostaglandins, thromboxanes, leukotrienes, and lipoxins. Literature data, however, suggest that also metabolites of the unsaturated fatty acid linoleic acid may be important in this respect. We have studied the formation and release of 9-hydroxy- and 13-hydroxy-linoleic acid (9-HODE and 13-HODE) by enriched populations of human peripheral blood neutrophils, eosinophils, basophils, monocytes, and lymphocytes. We demonstrate that the eosinophil preferentially produces 13-HODE, whereas the other cell types produce equal amounts of 9-HODE and 13-NODE. The biological significance of these findings is discussed.