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Acta Veterinaria Scandinavica 1977The effect of intrauterine iodine infusion on estrous cycle length was studied in four cows. The infusions were performed at various times of the estrous cycle: early,...
The effect of intrauterine iodine infusion on estrous cycle length was studied in four cows. The infusions were performed at various times of the estrous cycle: early, middle, late, and during luteolysis. Blood samples were drawn every third hour from the jugular vein. Progesterone and 15-keto-13,14-dihydroprostaglandin F (the main metabolite of PGF) were measured to monitor luteal activity and prostaglandin release. No release of prostaglandins was observed immediately following intrauterine infusion. Infusion in two cows on day 5 of the estrous cycle resulted in prostaglandin release after 54 and 69 hrs., respectively, followed by luteal regression and the occurrence of estrus at approx. five days after infusion. Infusions performed on days 11 or 12 resulted in prostaglandin release after 147 and 120 hrs., respectively, followed by luteolysis and heat after a 19 day estrous cycle. Infusion in two cows at days 16 and 17 resulted in prostaglandin release after 117 hrs. in both animals. One cycle was prolonged whereas the other cycle was normal in duration. One cow infused on day 20 following the occurrence of the first prostaglandin surge had a cycle length of 26 days, whereas another cow infused on day 20 was not affected because luteolysis was essentially complete by the time of infusion. One animal infused on day 5 did not respond to the iodine infusion. In this animal, however, the corpus luteum was not completely developed prior to the infusion. From this study it can be concluded: 1) intrauterine iodine infusions performed after the development of a progesterone secreting corpus luteum result in prostaglandin release within three to six days with the subsequent occurrence of luteolysis; 2) luteolysis was in all cases observed in connection with prostaglandin F release of the same order of magnitude and duration as during normal luteolysis. kw|Keywords|k]prostaglandin release; k]progesterone; k]cow; k]es trous cycle; k]iodine infusion
Topics: Animals; Cattle; Corpus Luteum; Estrus; Female; Injections; Iodine; Pregnancy; Progesterone; Prostaglandins F; Time Factors; Uterus
PubMed: 560113
DOI: 10.1186/BF03548456 -
Proceedings of the National Academy of... Aug 2003Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely...
Prostaglandins are involved in a wide variety of physiological and pathophysiological processes, but the mechanism of prostaglandin release from cells is not completely understood. Although poorly membrane permeable, prostaglandins are believed to exit cells by passive diffusion. We have investigated the interaction between prostaglandins and members of the ATP-binding cassette (ABC) transporter ABCC [multidrug resistance protein (MRP)] family of membrane export pumps. In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2. In contrast, MRP1, MRP2, MRP3, and MRP5 did not transport PGE1 or PGE2. The MRP4-mediated transport of PGE1 and PGE2 displayed saturation kinetics, with Km values of 2.1 and 3.4 microM, respectively. Further studies showed that PGF1alpha, PGF2alpha, PGA1, and thromboxane B2 were high-affinity inhibitors (and therefore presumably substrates) of MRP4. Furthermore, several nonsteroidal antiinflammatory drugs were potent inhibitors of MRP4 at concentrations that did not inhibit MRP1. In cells expressing the prostaglandin transporter PGT, the steady-state accumulation of PGE1 and PGE2 was reduced proportional to MRP4 expression. Inhibition of MRP4 by an MRP4-specific RNA interference construct or by indomethacin reversed this accumulation deficit. Together, these data suggest that MRP4 can release prostaglandins from cells, and that, in addition to inhibiting prostaglandin synthesis, some nonsteroidal antiinflammatory drugs might also act by inhibiting this release.
Topics: Adenosine Triphosphate; Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Transport; Cell Line; Cell Membrane; Diffusion; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Humans; Insecta; Multidrug Resistance-Associated Proteins; Prostaglandins; Prostaglandins A; Prostaglandins F; RNA Interference; RNA, Small Interfering; Ribosomal Proteins; Thromboxane B2; Time Factors
PubMed: 12835412
DOI: 10.1073/pnas.1033060100 -
American Journal of Obstetrics and... Dec 1987This study was undertaken to examine the effects of intrauterine infection and preterm labor on the amniotic fluid concentrations of prostaglandins in women with... (Comparative Study)
Comparative Study
This study was undertaken to examine the effects of intrauterine infection and preterm labor on the amniotic fluid concentrations of prostaglandins in women with premature rupture of the membranes. Amniotic fluid was obtained from four groups of patients with premature rupture of the membranes: group 1, patients without labor or infection; group 2, patients with labor but without infection; group 3, patients with an intra-amniotic infection but without labor; group 4, patients with both infection and labor. Prostaglandins E2 and F2a were measured by radioimmunoassays. Preterm labor, in the absence of infection, was not associated with significant increases in amniotic fluid concentrations of prostaglandins. Women with preterm labor and intra-amniotic infections had higher amniotic fluid concentrations of prostaglandins than women with preterm labor in the absence of infection or women with intra-amniotic infection in the absence of labor. These observations are compatible with the participation of prostaglandins in the mechanisms of onset of preterm labor associated with intra-amniotic infection.
Topics: Adult; Amniotic Fluid; Bacterial Infections; Dinoprost; Dinoprostone; Female; Fetal Membranes, Premature Rupture; Humans; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications, Infectious; Prostaglandins; Prostaglandins E; Prostaglandins F
PubMed: 3480691
DOI: 10.1016/s0002-9378(87)80245-4 -
The Journal of Physiology May 19781. The gastric juice outputs of acid, pepsin, PGE and PGF, and the plasma concentrations of PGE and PGF have been measured in response to I.V. infusions of pentagastrin,...
1. The gastric juice outputs of acid, pepsin, PGE and PGF, and the plasma concentrations of PGE and PGF have been measured in response to I.V. infusions of pentagastrin, histamine and insulin in the conscious cat. 2. There were significant correlations between the output of gastric acid and gastric outputs of both PGE and PGF during secretion produced by all stimulants. Furthermore, there were similar significant correlations between the gastric outputs of pepsin and both PGE and PGF. However, during insulin stimulation there was significantly more pepsin output per unit PGE or PGF output than during either pentagastrin or histamine stimulation. 3. The correlations between the outputs of gastric acid and both PGE and PGF were similar during pentagastrin and insulin stimulation whereas those between acid and PGE and PGF altered during the infusion of histamine. 4. It is concluded that these data partially, but not entirely, support the hypothesis that local release of prostaglandins may act as a negative feed-back mechanism on gastric acid secretion. 5. Plasma prostaglandin concentration did not correlate with changes in acid or pepsin secretion.
Topics: Animals; Cats; Gastric Juice; Histamine; Insulin; Pentagastrin; Pepsin A; Prostaglandins E; Prostaglandins F; Secretory Rate; Stimulation, Chemical
PubMed: 353256
DOI: 10.1113/jphysiol.1978.sp012316 -
The Journal of Physiology May 19881. The ability of oxytocin and prostaglandin F2 alpha (PGF) to induce contraction in guinea-pig myometrium in calcium-free solution was studied in an attempt to assess...
1. The ability of oxytocin and prostaglandin F2 alpha (PGF) to induce contraction in guinea-pig myometrium in calcium-free solution was studied in an attempt to assess the extent to which intracellular calcium stores could be released by these two agonists. Both longitudinal and circular muscle layers were studied separately and the effects of gestational age were also examined. 2. In longitudinal strips, the responses to oxytocin and PGF in the absence of external calcium decreased progressively throughout gestation. Responses of circular strips to both agonists were unchanged throughout pregnancy, until day 64, when no response to PGF could be elicited. 3. Pre-treatment with high potassium (and normal calcium) increased the responses to the agonists in calcium-free medium while pre-treatment with beta-adrenoceptor agonists had no effect on responses to oxytocin or PGF. 4. Responses to both agonists decreased with time in calcium-free solution suggesting a loss of calcium from stores with a half-time of 3 min. The rate of the decline in the responses was the same in both muscle layers and did not change with gestational age. 5. In the presence of lanthanum contractions evoked by oxytocin, but not PGF, were augmented 2-3-fold. This potentiation of the response to oxytocin occurred in both muscle layers and throughout gestation. 6. Each agonist evoked only one response in calcium-free solution containing EGTA. The response to PGF in longitudinal strips following a challenge with oxytocin was reduced, compared with the response to PGF when applied first while the response to oxytocin in these strips was unchanged following exposure to PGF. In circular strips neither oxytocin- nor PGF-induced contractions were altered following prior exposure to the other agonist. 7. It is concluded that oxytocin and PGF operate via two distinct mechanisms to release intracellularly stored calcium in both longitudinal and circular components of the guinea-pig myometrium and a hypothesis to explain the results is presented.
Topics: Animals; Calcium; Calcium Channel Blockers; Carbachol; Dinoprost; Female; Guinea Pigs; Myometrium; Oxytocin; Pregnancy; Pregnancy, Animal; Prostaglandins F; Uterine Contraction
PubMed: 3165444
DOI: 10.1113/jphysiol.1988.sp017065 -
Drug Design, Development and Therapy 2016The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels. (Comparative Study)
Comparative Study
AIM
The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels.
METHODS
Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase).
RESULTS
The IC50 values for Lumigan UD (bimatoprost 0.3 mg/mL), Monoprost (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively.
DISCUSSION
All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost.
Topics: Administration, Ophthalmic; Bimatoprost; Blood Platelets; Dose-Response Relationship, Drug; Drug Compounding; Glaucoma; Humans; Latanoprost; Ophthalmic Solutions; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Prostaglandins F; Prostaglandins F, Synthetic
PubMed: 27994439
DOI: 10.2147/DDDT.S117806 -
Molecules (Basel, Switzerland) Jan 2017Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the...
Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.
Topics: Antihypertensive Agents; Chemistry Techniques, Synthetic; Dinoprost; Glaucoma; Molecular Structure; Ocular Hypertension; Prostaglandins F
PubMed: 28146132
DOI: 10.3390/molecules22020217 -
Biology of Reproduction Jul 2007To study the role of endothelial factors in luteal function, the dynamic profiles of genes for endothelin 1 (EDN1), its receptor subtypes, EDNRA and EDNRB, and...
To study the role of endothelial factors in luteal function, the dynamic profiles of genes for endothelin 1 (EDN1), its receptor subtypes, EDNRA and EDNRB, and angiotensin converting enzyme (ACE) were examined in corpora lutea (CL) obtained from rabbits on Days 4 and 9 of pseudopregnancy after prostaglandin (PG) F2alpha analogue (alfaprostol) treatment. The cell type distribution of EDN1 in the ovaries and its mechanisms of actions in vitro and in vivo were also studied. Positive immunostaining for EDN1 was localized in the luteal and endothelial cells, in granulosa cells of the follicles, and in the ovarian epithelium. The basal mRNA levels for EDNRA, EDNRB, and ACE were lower (P = 0.01) in Day-4 CL than in Day-9 CL, whereas those for EDN1 did not differ between these two time-points. On Day 4, the luteal EDN1, EDNRA, EDNRB, and ACE mRNA levels were similarly increased two-fold (P = 0.01) 1.5 h after alfaprostol injection, and did not show further changes in the subsequent 24 h. On Day 9, alfaprostol challenge transiently up-regulated (P = 0.01) the luteal ACE transcripts at 1.5 h, and those of EDN1 at 1.5 h and 3 h, whereas the EDNRA and EDNRB transcript levels remained unchanged during the course of luteal regression. EDN1 decreased (P = 0.01) progesterone release and increased (P = 0.01) PGF2alpha secretion and NOS activity via the PLC/PKC pathway in Day-9 CL, but not in Day-4 CL, cultured in vitro. EDN1-induced, but not alfaprostol-induced luteolysis, was blocked by cotreatment in vivo with the ACE antagonist captopril. These findings support the hypothesis that PGF2alpha regulates luteolysis through intraluteal activation of the renin-angiotensin/EDN1 systems in CL that have acquired luteolytic competence.
Topics: Animals; Biomarkers; Corpus Luteum; Dinoprost; Endothelin-1; Female; Luteolysis; Ovary; Peptidyl-Dipeptidase A; Prostaglandins F; Pseudopregnancy; Rabbits; Receptors, Endothelin
PubMed: 17360961
DOI: 10.1095/biolreprod.106.055889 -
British Journal of Cancer Jun 1985Prostaglandin F2 alpha (PGF2 alpha) was determined by radioimmunoassay in 57 breast carcinomata, 16 fibroadenomata, and 33 sclero-cystic-disease (SCD) specimens. In 41...
Prostaglandin F2 alpha (PGF2 alpha) was determined by radioimmunoassay in 57 breast carcinomata, 16 fibroadenomata, and 33 sclero-cystic-disease (SCD) specimens. In 41 cases of carcinoma and 10 cases of fibroadenoma, histologically non-malignant tissue was also obtained from the same breast. PGF2 alpha levels were significantly elevated in breast cancer when compared with the normal tissues and benign diseases (P less than 0.005 for each group). High PGF2 alpha levels were positively correlated with differentiation, positive oestrogen and progestagen receptor status, and low mitotic index. Tumours with good prognosis (less than 20 mm, negative lymph nodes, some degree of differentiation) showed significantly higher PGF2 alpha levels than tumours with a bad prognosis (greater than 20 mm, positive nodes and undifferentiated). A tendency for elevated PGF2 alpha levels was observed with negative lymphatic permeation, postmenopausal status, low grade of nuclear and cellular polymorphism and high degree of elastosis and fibrosis. No correlation was observed between PGF2 alpha levels and host-cell reaction. Plasma levels of 15-keto-13, 14-dihydro-PGF2 alpha were not elevated in cancer patients when compared with the SCD-group. The present study demonstrates that PGF2 alpha levels are high in tumours with good prognosis. However, since other authors have suggested that a high PGE2 production is a bad prognostic index, it is possible that conversion of PGE2 to PGF2 alpha by 9-keto-reductase explains this relationship. Nevertheless, the presented results question the unrestricted use of prostaglandin-synthesis-inhibitors in the treatment of breast cancer.
Topics: Adenofibroma; Adult; Age Factors; Aged; Breast; Breast Diseases; Breast Neoplasms; Dinoprost; Female; Humans; Menopause; Middle Aged; Prostaglandins F; Radioimmunoassay; Receptors, Estrogen; Receptors, Progesterone
PubMed: 3859318
DOI: 10.1038/bjc.1985.128 -
Advances in Therapy Apr 2015The aim of the present study was to compare the confocal and clinical features of newly diagnosed glaucoma patients receiving unpreserved prostaglandins (tafluprost)... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The aim of the present study was to compare the confocal and clinical features of newly diagnosed glaucoma patients receiving unpreserved prostaglandins (tafluprost) versus preserved prostaglandins (latanoprost).
MATERIALS AND METHODS
40 patients were randomized to tafluprost 0.0015% (20 patients; 32 eyes) or latanoprost 0.005% + benzalkonium chloride 0.02% (20 patients; 35 eyes) once daily for 1 year. Inclusion criteria were new glaucoma diagnosis, and no ocular treatments for 6 months before the study. Patients were evaluated at baseline and every 3 months with a complete ophthalmologic evaluation, Schirmer's test, break-up time test, confocal microscopy of the central cornea, and measurement of intraocular pressure (IOP). Investigators were masked to treatment. Both eyes were analyzed if they fulfilled inclusion criteria. Treatments and changes between follow-up and baseline were compared by analysis of variance (ANOVA), t test and Chi-square test.
RESULTS
At baseline, the two groups had similar age, ocular surface and confocal findings; keratocyte activation was present in 40%, branching pattern in 85%, and beading in 75%, with no inter-group differences. At follow-up, no significant clinical changes were detected, apart from a drop of IOP by 3.6-4.2 mmHg in the two groups (p < 0.001, with no difference between treatments). Despite inter-treatment ANOVA for confocal microscopy being negative, subtle changes were present. During follow-up, all eyes without nerve branching pattern at baseline progressively developed it when treated with latanoprost, whereas no change occurred using tafluprost treatment (p = 0.05). None of the eyes without beading at baseline developed it at the end of the study in the tafluprost group, whereas beading did occur in 75% of patients treated with latanoprost (p = 0.05). Both treatments were associated with increased keratocyte activation at follow-up; the change from baseline was statistically significant after month 3 with latanoprost (p = 0.02) and after month 6 with tafluprost (p = 0.04).
CONCLUSIONS
The two study treatments had similar clinical effects, but tafluprost had a more favorable profile for some confocal parameters of the cornea.
FUNDING
Merck Sharp & Dohme International.
Topics: Administration, Ophthalmic; Aged; Aged, 80 and over; Antihypertensive Agents; Cornea; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic
PubMed: 25893514
DOI: 10.1007/s12325-015-0205-5