2α Levels Research Articles

Modulation of prostaglandin production by nitric oxide in astroglia

We examined the effects of exogenous nitric oxide (NO) on prostaglandin production in fetal ovine astroglia. Astroglia in secondary culture grown in 12 well plates were exposed to medium alone or medium containing 10 ng/ml interleukin 1α (IL1α), in the presence or absence of 10 and 100 μM sodium nitroprusside (SNP). Sodium nitroprusside is a NO donor. Prostaglandin F 2α (PGF 2α) levels were determined by enzyme immunoassay after 4 h of medium and/or drug application. Application of 100 μM SNP reduced basal levels of PGF 2α from 530 ± 48 pg/ml (mean ± SEM) ( n = 9) to 248 ± 60 pg/ml ( n = 8) ( P < 0.05). In IL1α treated cells, PGF 2α levels were 846 ± 109 pg/ml ( n = 9) ( P < 0.05, compared to basal levels) in the absence and 567 ± 122 pg/ml ( n = 9) in the presence of 100 μM SNP ( P < 0.05, compared to IL1α alone). We tested whether effects of exogenous NO on PGF 2α levels would be influenced by elimination of endogenously produced NO. Inhibition of NO synthase with 100 μM N G-nitro- l-arginine-methyl ester ( l-NAME) did not affect PGF 2α levels during basal conditions, or affect reductions in PGF 2α levels during application of 100 μM SNP. In addition, l-NAME application did not affect IL1α-induced increases in PGF 2α levels or reductions in PGF 2α levels with coapplication of 100 μM SNP. In contrast to the higher dose, application of 10 μM did not significantly affect PGF 2α levels. In summary, application of 100 μM SNP reduces basal production of PGF 2α and attenuates increases in PGF 2α levels with IL1α application.

Effect of mifepristone and antiestrogens on uterine PGF 2α and PGE 2 concentrations in ovariectomized and pregnant rats

Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF 2α and PGE 2). Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE 2 or PGF 2α concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF 2α concentration, resulting in an increase in the PGF 2α/PGE 2 ratio. Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF 2α concentrations and in the PGF 2α/PGE 2 ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE 2 concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF 2α/PGE 2 ratio. Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on days 7, 8 and 9 of pregnancy induced an increase in PGF 2α levels without affecting uterine PGE 2 concentration. The changes in uterine PGF 2α concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF 2α/PGE 2 ratio. The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only “pure” antiestrogen among those tested. The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF 2α and/or decrease PGE 2 concentrations, resulting in an alteration of PGF 2α/PGE 2 ratio. These findings suggest that there exists a critical balance of PGF 2α to PGE 2 concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy.

Effect of Toxoplasma gondii infection on the development of pregnancy and on endocrine foetal-placental function in the goat

The effect of Toxoplasma gondii inoculation on pregnancy and on endocrine foetal-placental function in pregnant goats was studied. Five susceptible goats were inoculated subcutaneously with T. gondii bradyzoites at 71±2 days of gestation. Another five goats were used as controls. Plasma was analysed for progesterone, oestrone sulphate and 15-ketodihydro-PGF 2α. The condition of the foetuses was monitored by real-time ultrasonography. All inoculated goats aborted or delivered stillborn or weak kids 54–73 days after inoculation. None of the goats showed signs of general disease. In cases of foetal death, the ultrasound examination revealed that death occurred between day 1 and 12 before abortion or birth. The appearance of the foetuses varied from fresh to mummified, depending on the number of days between foetal death and expulsion. All five goats became serologically positive to T. gondii after inoculation. None of the goats used as controls aborted, but one goat delivered one mummified and one weak kid for unknown reasons. In inoculated animals an increase in 15-ketodihydro-PGF 2α levels in plasma and a subsequent tendency to a decrease in oestrone sulphate levels were observed from about day 40 after inoculation and until abortion or birth. High levels of 15-ketodihydro-PGF 2α were seen after foetal death. High levels of 15-ketodihydro-PGF 2α were not always followed by a drop in progesterone levels. The mean level of progesterone was slightly decreased after inoculation and onwards. The pattern of progesterone levels around abortion in the inoculated goats was very similar to the pattern around parturition in the control goats. However, 15-ketodihydro-PGF 2α levels were higher both before and after abortion in inoculated goats than in control goats. The level of oestrone sulphate did not increase in the inoculated group before abortion in contrast to the level in goats which delivered healthy kids. The patterns of changes in levels of 15-ketodihydro-PGF 2α and oestrone sulphate in inoculated animals indicate that the endocrine foetal-placental function was disturbed in most of the inoculated goats, probably due to the injury caused by the establishment and development of T. gondii infection in the placenta and foetus.

A reliable and sensitive enzyme immunoassay method for measuring 8-isoprostaglandin F 2α: a marker for lipid peroxidation after experimental brain injury

The objectives of this study were to determine (1) if levels of 8-isoprostaglandin F 2α (8-isoPGF 2α), a non-enzymatically produced prostaglandin, were increased after cortical contusion and (2) if enzyme immunoassay (EIA) could be used to quantify 8-isoPGF 2α levels. 24 h after the contusion there was a significant rise in 8-isoPGF 2α compared to control levels. The levels returned to baseline by 72 h postinjury. The results show that this EIA method is a reliable and sensitive technique for measuring brain lipid peroxidation.

Influence of underfeeding on the spontaneous contraction and on metabolism of labelled arachidonic acid in uteri isolated from intact and ovariectomized rats

The effects of restricted diet (50% of the normal intake during 25 days) on the isometric developed tension (IDT), and on the metabolism of labelled arachidonic acid in uteri from intact and spayed (25 days) rats, were studied. Underfeeding produced a fall in the contractile activity of intact rats, while in ovariectomized rats contractile activity increased. Indomethacin reduced uterine contractile activity in all the cases under study. The metabolism of arachidonic acid into different eicosanoids, PGE 2, PGF 2α, 6-keto-F 1α, and TXB 2, showed that the restricted diet diminished PGE 2 and PGF 2α levels in intact rats, significantly. The reduction in uterine contractile activity and reduced levels of the arachidonic acid metabolites, PGE 2 and PGF 2α, were not seen in ovariectomized animals.

Elevated plasma levels of hyaluronic acid indicate endothelial cell dysfunction in the initial stages of alcoholic liver disease in the rat

Background/Aims: We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship between morphologic and functional indicators of endothelial cell dysfunction. Methods: Twelve groups of rats (4–5 rats/group) were fed the following diets: saturated fat and dextrose (SD), saturated fat and ethanol (SE), corn oil and dextrose (CD), corn oil and ethanol (CE). Four of the 12 groups were sacrificed at 2 weeks, four groups at 4 weeks and remaining four groups at 8 weeks. The following were evaluated at sacrifice: pathologic changes in the liver, endothelial cell proliferation using a monoclonal antibody to proliferating cell nuclear antigen, factor VIII-related antigen staining of endothelial cells in liver, plasma endotoxin, hyaluronan and prostaglandin F 2α. Results: Only CE rats at 4 and 8 weeks showed pathologic changes. The plasma levels of HA were significantly higher in the CE groups compared to the other groups at all time intervals studied. In the CE rats, a significant correlation was obtained between plasma endotoxin and hyaluronan ( r=0.84, p<0.01). Endotoxin levels also correlated significantly with the number of G 1/S arrested hepatic sinusoidal endothelial cells ( r=0.61, p<0.05). A role for prostaglandin F 2α, in causing endothelial dysfunction, was suggested by a significant correlation between plasma hyaluronan and prostaglandin F 2α levels ( r=0.95, p<0.01). Positive factor VIII related antigen staining of hepatic endothelial cells was seen in rats with high plasma hyaluronan levels. Conclusion: We propose that endotoxin, mediating part of its effect through prostaglandin F 2α, plays a role in hepatic sinusoidal endothelial cell G 1/S arrest. This morphologic change, associated with increased plasma hyaluronan levels, precedes capillarization in this model of alcoholic liver injury.

Prostaglandin Production and Ovulation during Exposure of Amphibian Ovarian Follicles to Gonadotropin or Phorbol Estr in Vitro

Experiments were carried out at different times of hibernation to ascertain whether prostaglandin is produced by Rana ovarian follicles during gonadotropin- or 12- O-tetradecanoylphorbol-13-acetate (TPA)-induced in vitro ovulation. Ovarian fragments were cultured in amphibian Ringer in the presence or absence of frog pituitary homogene (FPH, 0.05 gland/ml) or TPA (1 or 10 μ M). After various periods of culture, incidence of ovulation was determined and prostaglandia F 2α (PGF 2α) accumulated in culture medium was measured by radioimmunoassay. FPH and TPA increased PGF 2α levels in medium in a dose-dependent manner. The time course of PGF 2α secretion and ovulation by FPH or TPA treatment varied during the hibernation period. In early-hibernation, FPH stimulated neither PGF 2α secretion and ovulation, but both events took place several hours later than those observed in late-hibernation. Some fragments obtained in mid-hibernation and most obtained in late-hibernation spontaneously produced PGF 2α in vitro without FPH or TPA treatment and in some instance spontaneously ovulated. Furthermore, FPH or TPA increased PGF 2α levels further or accelerated the time course of secretion by such fragments. In late-hibernation, PGF 2α secretion induced with FPH or TPA increased simultaneously with or later than onset of ovulation. Exogenous cAMP (2.5 m M) or 1-(5-isoquinolinylsulfonyl)-2-methyliperazine 9H-7, 100 μ M), a PKC inactivator, markedly suppressed FPH- or TPA-stimulated PGF 2α secrettion and ovulation in mid-hibernation. Indomethacin (IM, 5 μg/ml) strongly suppressed TPA- or FPH-stimulated PGF 2α production by fragments but its effect on ovulation varied among animals and at different times. IM suppressed ovulation of some ovarian fragments obtained in mid-hibernation, but failed to suppress hormone-induced ovulation in late-hibernation. Cycloheximide (5 μg/ml) and actinomycin D (1 μg/ml) effectively suppressed FPH-stimulated PGF 2α production and ovulation, whereas actinomycin D reduced but failed to significantly suppress TPA-induced PGF 2α production in mid-hibernation. In general, effects of ovulation inhibitors exhibited strong seasonal variations and were less efficient as the breeding season approached. Taken together, the data suggest that elevated levels of PGF 2α are associated with spontaneous and hormone-induced ovulation, and PKC mediates gonadotropin induction of PGF 2α but not steroid synthesis in Rana ovaries.

Plasma 8-epi-PGF 2α levels are elevated in individuals with non-insulin dependent diabetes mellitus

This study reports plasma levels of a specific nonenzymatic peroxidation product of arachidonic acid, esterified 8-epi-PGF 2α, from healthy- and NIDDM individuals as an index of oxidative stress in vivo. Plasma 8-epi-PGF 2α was isolated by solid-phase extraction on a C,8 followed by an NH 2 cartridge and analyzed by GC-MS/NICI as PFB-ester/TMS-ether derivative. We found that the average concentration of esterified 8-epi-PGF 2α among NIDDM subjects (0.93 ± 0.07 nM, n = 39) was higher ( P < 0.0001, Mann-Whitney test) than in healthy individuals (0.28 ± 0.04 nM, n = 15). These data indicate that NIDDM is associated with increased plasma lipid peroxidation.

Protein kinases and prostaglandin production in ovine astroglia

We examined effects of interleukin-1α (IL-1α) and involvement of protein kinases on prostaglandin production in cultured ovine astroglia. Ovine astroglia were exposed to media alone, or 10 ngImL IL-1α and prostaglandin F 2α (PGF 2α levels were analyzed using enzyme immunoassay. Application of IL-1α augmented the production of PGF 2α at 4 h. Coapplication of H-7 (10–1000 μM) and staurosporine (0.1–10 μM), inhibitors of protein kinase C (PKC), blocked IL-1α-induced PGF 2α production. IL-1α increased cyclooxygenase (COX) activity while coapplication of staurosporine prevented an increase, implying that COX activity was dependent upon PKC activation. In contrast, forskolin, sodium nitroprusside, and cyclic nucleotide analogs alone did not affect prostaglandin production significantly, excluding the involvement of cAMPIcGMP-dependent protein kinases. Coapplication of quinacrine (10 μM) and bromophenacyl bromide (100 μM), inhibitors of phospholipase A 2 (PLA 2), prevented the IL-1α induced increases in PGF 2α production. Lastly, IL-1α increased labeled arachidonic acid (AA) release whereas coaddition of quinacrine (10 μM) attenuated increased AA release. Therefore, we propose that IL-la enhances prostaglandin production by ovine astroglia via steps involving activation of PKC and increased activity of COX and PLA 2.

Rapid induction of prostaglandin synthesis in piglet astroglial cells by interleukin 1α

We examined effects of interleukin 1α (IL-1α) on prostaglandin production in piglet cultured astroglia. Immuno-and morphologically identified polymorphic and process-bearing astrocytes were collected from cerebral cortex and white matter from piglets (1–3 days of age). Levels of Prostaglandins were determined using enzyme immunoassay. Baseline levels for prostaglandin (PG) F 2α, were 631 ± 332 pg/ml and increased to 1417 ± 353 pg/ml 20 min after addition of 11 μg/ml IL-1α ( p < 0.05) and to 2280 ± 391 pg/ml 20 min after addition of 22 μg/ml IL-1α ( p < 0.05) ( n = 7). Only small amounts of 6-ketoPGF 2α or PGE 2 were detected in medium under baseline conditions or in the presence of IL-1α. Medium alone did not change PGF 2α levels ( n = 3). Coapplication of cycloheximide (10 −3 M) blocked the increase in PGF 2α ( n = 3). We conclude that IL-1α causes a rapid increase in prostaglandin production by astroglia, and this process involves a step requiring continued or increased protein synthesis.

A comparison of serum and vaginal dialysate concentration of 13,14-dihydro-15-keto-PGF 2α in women undergoing 1st trimester therapeutic abortions

13,14-Dihydro-15-keto-PGF 2α(PGFM) levels in serum and vaginal secretion, before, one hour, and 24 hours post abortion were measured in 13 women from 8 to 12 weeks pregnant. The mean metabolite levels in the blood were 61.2 pg/ml pre-termination, 73.1 pg/ml and 121.4 pg/ml one hour and 24 hours post-termination. The vaginal dialysate means were 136.7 pg/ml, 425.7 pg/ml, and 211.7 pg/ml respectively.

Effect of ibuprofen on regional eicosanoid production and neuronal injury after forebrain ischemia in rats

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups ( n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B 2 (TxB 2), 6-keto-PGF 1α and PGF 2α in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats ( >n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB 2, 6-keto-PGF 1α and PGF 2α increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB 2 and PGF 2α increased in both CN and HPC. Levels of 6-keto-PGF 1α increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB 2 and PGF 2α levels in both CN and HPC and decreased 6-keto-PGF 1α levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals ( n = 5), ibuprofen was administered after probe insertion. Only PGF 2α levels were measured in this group. Increased levels of PGF 2α comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF 2α were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibuprofen treated animals. This protective effect of ibuprofen was most clearly evident in the CA3 sector of the HPC. The data suggest that metabolism of arachidonic acid by cylooxygenase may contribute to post-ischemic neuronal injury, though the relative contributions of eicosanoids per se and of free radicals remains undefined.

‘Cross-talk’ between phospholipase C and adenylyl cyclase involves regulation of G-protein levels in GH 3 rat pituitary cells

We have investigated the possibility that adenylyl cyclase (AC) activity and membrane protein levels of the α-subunits of the stimulatory and inhibitory G-proteins of AC (G sα and G i−2α) in cultured prolactin-producing rat pituitary adenoma cells (GH 3 cells) are modulated by phospholipase C (PLC)-generated second messengers. Pretreatment of cells (6–48 h) with ionomycin (1 μM) or 1-oleoyl-2-acetylglycerol (OAG; 1μM) showed that ionomycin regulated G sα levels in a time-dependent, biphasic manner; a two-fold increase followed a 40% initial reduction, while OAG lowered G sα levels by more than 50% at all time-points. G i−2α levels remained unchanged by both pretreatments. OAG, but not ionomycin, increased basal AC activity without increasing enzyme protein levels. Alterations in AC responsiveness to peptide hormones (e.g. thyroliberin and vasoactive intestinal peptide) correlated to membrane G s protein α-subunit content. These results demonstrate the involvement of G-protein translation regulation as one mechanism of ‘cross-talk’ between the PLC- and AC-dependent signalling pathways.

A possible involvement of prostaglandin F 2α (PGF 2α) in Rana esculenta ovulation: Effects of mammalian gonadotropin-releasing hormone on in vitro PGF 2α and 17β-estradiol production from ovary and oviduct

The present work studied the PGF 2α and 17β-estradiol plasma levels during ovulation, and the in vitro effects of mammalian gonadotropin-releasing hormone (mGnRH) on ovarian and oviductal production of prostaglandin F 2α (PGF 2α) and 17β-estradiol during four different stages of the annual sexual cycle in water frog, Rana esculenta. Plasma levels of PGF 2α increased in ovulating frogs, with respect to preovulatory and postovulatory levels, while estradiol did not change. In addition, mGnRH increased PGF 2α and 17β-estradiol in the incubation media of ovaries taken during the recovery stage. Moreover, mGnRH increased PGF 2α in incubation media of oviducts collected during the reproductive stage. These findings suggest that PGF 2α could be involved in the control of egg deposition in the female R. esculenta.

In vivo release of 15-hete and other arachidonic acid metabolites in nasal secretions during early allergic reactions

The purpose of this study is to examine to “in vivo” release of 15-HETE and other arachidonic acid metabolites in nasal secretions following a challenge with “Dermatophagoides Pteronyssinus” in patients with allergic rhinitis and non-allergic controls. In addition, we examine the effects of a membrane stabilizer, such a sodium cromoglycate, on these metabolites Thirteen allergic subjects and seven healthy controls are studied. 15-HETE , peptide leukotrienes, LTB 4 PGD 2, PGE 2 and PGF 2α levels are evaluated before and after nasal challenge in sodium cromoglycate treated and untreated subjects. This study provides “in vivo” evidence that the pathophysiological responses to nasal antigen challenge could be related to the release of 15-HETE as well as other arachidonic acid metabolites, mainly arising from the lipoxygenase pathway.

Effects of mammalian gonadotropin-releasing hormone on plasma level of prostaglandin F 2α in the water frog, Rana esculenta

The present investigation was performed to evaluate the effects of mammalian gonadotropin-releasing hormone (mGnRH) on prostaglandin F 2α (PGF 2α) plasma level in adult male and female water frog, Rana esculenta, during three different periods of the reproductive cycle: recovery period (October), breeding period (May), and postreproductive period (June). Intact, hypophysectomized (HYP), gonadectomized (GON), and hypophysectomized-and-gonadectomized (HYP/GON) animals were injected with 0.6 μg of mGnRH and sacrificed 1 hr and 5 hr after peptide administration. Some of each of the groups were sacrificed without having received mGnRH. PGF 2α plasma levels were assessed by radioimmunoassay. Hypophysectomy induced a significant increase of PGF 2α levels in October and June males. mGnRH induced a significant increase of PGF 2α plasma levels only in HYP and HYP/GON frogs. The tissue target of this GnRH action is, at present, unknown, although interrenals could be putative responsive tissues. At present, it is also difficult to assign any physiological role to observed phenomena unless to suppose that the pituitary inhibition is not constant throughout the year. It cannot be excluded that the prostaglandin induction depends on a local paracrine action of GnRH, which could be performed outside any pituitary control.

Inhibition of the first ovulation and ovarian prostaglandin F 2α metabolism by danazoi in rats

The present study was conducted to investigate the mode of action of danazoi by monitoring the first ovulation, serum luteinizing hormone (LH) levels and ovarian prostaglandin (PC) F 2α metabolism in pregnant mare serum gonadotropin (PMSG)-primed immature female rats. When danazoi (750 mg/kg) was given p.o. once a day for 5 days (day 24–28), the occurrence of the first ovulation, the increase in capacity to.form 13,14-dihydro-PGF 2α and PGF 2α levels induced by PMSG (5 IU) injected on day 26 were clearly inhibited on day 29. Danazoi also markedly suppressed the LH surge occurring on day 28. Although the danazol-induced blockage of ovulation was restored by injection of human chorionic gonadotropin, the number of oocytes was significantly decreased as compared with that of controls. The present data indicate that the inhibitory actions of danazoi on ovulation and ovarian PGF 2α metabolism may occur via some direct effects on the ovary in addition to the suppression of gonadotropin release from the pituitary gland.

Fatty acid and prostaglandin metabolism in children with diabetes mellitus. II. — The effect of evening primrose oil supplementation on serum fatty acid and plasma prostaglandin levels

Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E 2 (PGE 2) and F 2α (PGF 2α) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE 2 and PGF 2α levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capusles (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE 2 and PGF 2α levels. After administration of 4 capsules daily the DGLA levels increased and PGE 2 levels decreased significantly (p < 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE 2 and PGF 2α levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

Prostaglandin-F 2α levels in normal saline-induced mid-trimester abortions

In 20 mid-trimester abortion seekers induced by extra-amniotic instillation of normal saline, serial estimation of prostaglandin F 2α (PGF 2α) in the plasma and extra-ovular space were carried out. It was observed that PGF 2α was undetectable in both plasma and the extra-ovular space prior to the onset of induction, and was first detected in the extra-ovular fluid 2 hours after the onset of induction, prior to oxytocin infusion. In the subsequent samples, the prostaglandin concentration in plasma as well as in the extra-ovular fluid was found to rise, with levels in the latter showing a more significant rise with time as compared to the former. Thus, this study confirms the hypothesis that the mechanism of action of extra-ovular normal saline instillation in mid-trimester termination of pregnancy is the result of separation of fetal membranes from the uterine wall, leading to the release of prostaglandins which, in turn, causes uterine contractions leading to abortion.

Phenobarbital increases rat hepatic prostaglandin F 2α, glutathione S-transferase activity and oxidative stress

Eight-week-old female F344 N rats were fed 3.0 or 6.0% of calories (kcal%) as linoleate with or without 0.05% phenobarbital (PB) for 35 days. PB treatment increased glutathione S-transferase (GST) activity by 80% and prostaglandin (PG) F 2α levels 4-fold (p < 0.05). PB decreased hepatic α-tocopherol significantly. Hepatic linoleate was decreased by PB in rats fed 6 kcal% but not 3 kcal% linoleate. Increased dietary linoleate had no significant effect on hepatic PGF 2α or α-tocopherol levels or GST activity. This study suggests that PB hepatotoxicity and tumor-promoting ability may be mediated, at least in part, by PGF 2α. PB's effect on PGF 2α could be a result of both GST-mediated prostaglandin synthesis and oxidative stress. The removal of significant amounts of hepatic α-tocopherol during oxidative stress induced by PB might diminish endogenous inhibition of hepatic PG synthesis by a-tocopherol.