Experimental induction of luteal cyclicity in roe deer (Capreolus capreolus).
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Concentrations of progesterone and luteinizing hormone in plasma were analysed for two consecutive years in samples from nonpregnant female roe deer. Three animals were treated with monthly prostaglandin injections (325 micrograms cloprostenol) from October 1989 to April 1990 and from October 1990 to March 1991, and three were kept as controls. In control animals, a small increase in progesterone concentrations in July 1990 occurred at the same time as the commencement of the rut in other husbanded roe deer. In prostaglandin-treated animals, progesterone concentration was high at the time of the rut and remained so until late February 1990. After the next rut (August 1990), progesterone concentration remained high until March 1991. Between October and February-March, injections of prostaglandins induced dramatic, but temporary (lasting 72 h), decreases in plasma progesterone concentrations, indicating luteal regression and subsequent ovulation. We infer that roe deer can ovulate repeatedly and should therefore not be regarded as an obligate monoestrous species. (+info)
Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide.
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PURPOSE: To investigate long-term changes in the anterior segment of primate eyes treated for one year with different prostaglandin agonists and a prostamide. The results were compared with those obtained after vehicle treatment and in untreated controls. METHODS: Sixteen young cynomolgus monkeys were unilaterally topically treated for 1 year with either bimatoprost 0.03% (prostamide), sulprostone 0.03% (EP(3)/EP(1) agonist), AH13205 0.1% (EP(2) agonist), or latanoprost 0.005% (FP agonist), which all lower IOP in this species at the doses applied. Four animals were treated with the vehicle only. In all cases the left eye was treated, the right eye remained untreated. Six monkeys served as untreated controls. Sections from 4 quadrants each of the circumference of the eyes of 16 drug-treated, 4 vehicle-treated and 6 untreated control animals were investigated qualitatively and quantitatively using light- and electronmicroscopy. The area of widened spaces between ciliary muscle bundles, the number of nerve fiber bundles at the muscle tips, and the width and length of the ciliary muscle were quantitated. RESULTS: The general morphology of the ciliary muscle and trabecular meshwork was normal in appearance and shape in all animals, whereas some localized morphologic changes were observed in the drug-treated animals. The changes were found to be similar in all four treatment groups. In the ciliary muscle, there was a significant increase in optically empty spaces between muscle bundles in the anterior portion of the longitudinal and the reticular ciliary muscle compared with untreated and vehicle-treated control animals. Within these spaces, significantly more myelinated nerve fiber bundles were found in drug-treated compared with normal control animals. Ultrastructurally the spaces were partly covered by endothelial-like cells which, in some areas, were in contact with the basement membrane of the microvasculature. In all treatment groups, there were also changes in the trabecular meshwork region. Significant regional differences among the different quadrants of the eyes and quantitative differences between treatment groups were observed. The ciliary epithelium had a normal appearance in all treatment groups. CONCLUSIONS: After one year of treatment with different prostaglandins and a prostamide, uveoscleral outflow pathways are enlarged and appear organized. Conventional outflow routes were also affected. Long-term treatment with AH13205, latanoprost, sulprostone, or bimatoprost also induces sprouting of nerve fibers. (+info)
Upregulation of orphan nuclear receptor Nur77 following PGF(2alpha), Bimatoprost, and Butaprost treatments. Essential role of a protein kinase C pathway involved in EP(2) receptor activated Nur77 gene transcription.
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1. Using gene chip technology, we first identified that PGF(2alpha) (FP agonist) and Butaprost (EP(2) agonist) induced about a five-fold upregulation of Nur77 mRNA expression in hFP-HEK 293/EBNA and hEP(2)-HEK293/EBNA cells. Northern Blot analysis revealed that PGF(2alpha)- and Butaprost-induced upregulation of Nur77 expression are dose- and time-dependent. 2. Both PGF(2alpha) and Butaprost upregulated Nur77 gene expression through the protein kinase C (PKC) pathway. These data are the first showing a link between EP(2) receptor stimulation and protein kinase C activation. Calcineurin was found to be involved downstream of the PKC pathway in PGF(2alpha)-induced Nur77 expression, but not in Butaprost-induced Nur77 expression. 3. We also used Nur77 as a marker gene to compare the effects of PGF(2alpha), Butaprost, and Bimatoprost (a prostamide) on Nur77 expression in human primary trabecular meshwork and ciliary smooth muscle (SM) cells, which are target cells for antiglaucoma drugs. The results showed that PGF(2alpha) and Butaprost, but not Bimatoprost, induced upregulation of Nur77 expression in human TM cells. PGF(2alpha), but not Bimatoprost, dramatically induced upregulation of Nur77 mRNA expression in human ciliary SM cells, whereas Butaprost slightly upregulated Nur77 mRNA expression in SM cells. 4. Nur77 promoter deletion analysis indicated that PGF(2alpha), but not Bimatoprost, activated Nur77 promoter-luciferase reporter in hFP-HEK 293/EBNA cells. Butaprost was less efficacious in inducing Nur77 promoter-luciferase reporter activity in hEP(2)-HEK293/EBNA cells relative to PGF(2alpha) in the comparable assay. The data for Nur77 promoter functional analysis were matched to the Northern blot analysis. 5. It appears that PGF(2alpha) and Butaprost activate Nur77 transcription mechanisms through the activation of FP and EP(2) receptor-coupled signaling pathways, whereas Bimatoprost stimulates neither FP nor EP(2) receptors. (+info)
Concentrations of immunoreactive inhibin in ovarian and peripheral venous plasma and follicular fluid of Booroola ewes that are homozygous carriers or non-carriers of the FecB gene.
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No gene-specific differences were found during either the luteal or follicular phases of the oestrous cycle in the venous secretion rates of ovaries or in concentrations of immunoreactive inhibin in peripheral plasma between Booroola ewes that were homozygous carriers (BB) or non-carriers (++) of the FecB gene. In three experiments in which concentrations of plasma inhibin and follicle-stimulating hormone (FSH) were compared, gene-specific differences were noted for FSH (P less than 0.05), but no significant correlations were noted between FSH and inhibin for either genotype. Granulosa cells and follicular fluid, but not theca interna, stroma or corpora lutea, were the major intra-ovarian sites of inhibin; no gene-specific differences were noted for inhibin concentrations in follicular fluid or in any of the intra-ovarian tissues. The mean concentrations of inhibin in follicular fluid remained constant irrespective of follicular diameter whereas the mean total contents of inhibin increased significantly with increasing diameter (P less than 0.05). Inhibin secretion rates were four times higher in ovaries with oestrogen-enriched follicles (i.e. greater than or equal to 50 ng oestradiol ml-1) than in ovaries with no such follicles (P less than 0.01). Moreover, inhibin concentrations were higher in follicular fluid of oestrogen-enriched follicles than in those with low oestrogen (i.e. less than 50 ng ml-1; P less than 0.05). Ovariectomy resulted in a significant reduction in concentrations of immunoreactive inhibin from plasma (P less than 0.01). The residual plasma inhibin in some Booroola ewes was not associated with genotype. It is concluded that, although antral follicles are a major source of inhibin in Booroola ewes, immunoreactive inhibin is not associated with the FecB gene and is not responsible for the gene-specific differences in concentrations of FSH in plasma. (+info)
Studies using isolated uterine and other preparations show bimatoprost and prostanoid FP agonists have different activity profiles.
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1. The pharmacology of bimatoprost, a synthetic prostaglandin-amide, was examined in prostaglandin F(2alpha) (PGF(2alpha))-sensitive preparations. Bimatoprost potently contracted the rabbit isolated uterus (pEC(50)=7.92+/-0.16). In contrast, bimatoprost exhibited weak excitatory activity in human myometrium from pregnant and nonpregnant donors, mouse uterus, rat uterus, and endothelium-intact rabbit jugular veins, and did not stimulate DNA synthesis in mouse fibroblasts. 2. The possibility that the effects of bimatoprost may reflect partial agonism at prostanoid FP receptors was examined and the contractile effects of full agonists, 17-phenyl PGF(2alpha) (FP) and U-46619 (TP, a control), were determined in the absence and presence of 1 muM bimatoprost on the mouse uterus. Analyses of the agonist-agonist functional studies showed no antagonism, indicating that bimatoprost is not a partial agonist. 3. Bioassay metabolism studies of bimatoprost and latanoprost (FP receptor agonist prodrug) in the rabbit uterus were conducted using recipient mouse uterus. Results indicated that the potent responses to bimatoprost in the rabbit uterus are produced by the intact molecule and not by its putative free acid metabolite, 17-phenyl PGF(2alpha). Some hydrolysis of latanoprost to latanoprost free acid appears to have occurred in the rabbit uterus, according to biological detection. 4. The pharmacology of bimatoprost could not be explained by its interaction with known prostanoid FP receptors and was independent of species-, tissue-, or preparation-related factors. The potent contractile effects of bimatoprost in the rabbit uterus provide further pharmacological evidence for the presence of a novel receptor population that preferentially recognises bimatoprost. (+info)
Influence of a PGF2alpha-analogue, etiproston tromethamine, on the functional corpus luteum of dogs.
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To induce luteal regression-related abortion/delivery and treat pyometra in dogs, various PGF2alpha-analogues (PGAs) are administered, but a PGA most appropriate for clinical application in dogs, with a low incidence of side effects, is being investigated. In this study, we compared the effects of etiproston tromethamine (PGA-E), which has not been investigated in dogs, with those of cloprostenol (PGA-C), which is routinely used in dogs. A single dose of PGA-E at 100, 200, 400 or 800 microg or PGA-C at 12.5, 25, 50 or 100 microg was administered to beagles (n=5 per group) 25 days after ovulation, when the corpus luteum was in the functional phase. We compared the state of luteal regression by measuring plasma progesterone levels. As side effects, the incidences of salivation, vomiting, tachypnea, diarrhea and the drop in body temperature were investigated. In the 400-microg and 800-microg groups treated with PGA-E, the mean intervals from administration until luteal regression were 18.6 days and 31.2 days, respectively. In the dogs treated with 50 microg or more of PGA-C, luteal regression was noted 2 days after administration. The above side effects were observed for 3 hr after administration of PGA-E/PGA-C. In the dogs treated with 800 microg of PGA-E, the mean body temperature was 36.7 degrees C 4 hr after administration; hypothermia persisted. PGA-E may be less useful than PGA-C for promoting luteal regression in dogs in clinical application. (+info)
Effects of glaucoma drugs on ocular hemodynamics in normal tension glaucoma: a randomized trial comparing bimatoprost and latanoprost with dorzolamide [ISRCTN18873428].
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BACKGROUND: Reduced choroidal perfusion is hypothesized to play a role in the pathogenesis of normal tension glaucoma. Thus the impact of antiglaucomatous eye drops on ocular perfusion has been the focus of recent research and the subject of intensive investigations. The present study investigates whether topically applied latanoprost or bimatoprost influence ocular perfusion in patients with normal tension glaucoma and compares these effects with that changes detected after the treatment with dorzolamide. METHODS: Ocular hemodynamics were assessed by color Doppler imaging (CDI) shortly before and after a one-month treatment with either latanoprost, bimatoprost or dorzolamide. Primary end-points of the study were peak systolic and end-diastolic blood flow velocities in the short posterior ciliary artery (SPCA) under the new therapy. Intraocular pressure (IOP) and additional perfusion parameters in the SPCA and other retrobulbar vessels were tracked as observational parameters. n = 42 patients with normal tension glaucoma were enrolled in the study. RESULTS: Systolic and diastolic blood flow velocities in the SPCA showed no significant alteration after the treatment with latanoprost or bimatoprost. Dorzolamide lead to increase of peak systolic velocity. IOP was reduced by all three agents in a range reported in the literature. CONCLUSION: Topically applied latanoprost and bimatoprost act in a hemodynamically neutral manner and have the capability to lower IOP even in patients with normal tension glaucoma and low initial IOP level. Dorzolamide accelerates blood flow in systole. None of the tested compounds has a negative impact on hemodynamics in the short posterior ciliary arteries. (+info)
Effects of the combination of bimatoprost and latanoprost on intraocular pressure in primary open angle glaucoma: a randomised clinical trial.
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AIMS: To evaluate the effect of the combination of bimatoprost and latanoprost on intraocular pressure (IOP) in primary open angle glaucoma (POAG). METHODS: An open label randomised clinical trial was conducted, which included 18 glaucomatous patients (36 eyes). In the first 4 weeks, latanoprost 0.005% was prescribed for both eyes of the patients and any other antiglaucoma medication was discontinued. In the next 4 weeks (phase 1), bimatoprost 0.03% was combined with latanoprost in one randomly assigned eye (case eye) of each patient. In the next 4 weeks (phase 2), bimatoprost was discontinued in the case eyes, while bimatoprost was substituted for latanoprost in the fellow eye (control eye). The IOP was measured at the end of the first 4 weeks (baseline measurement) and weekly during phases 1 and 2. RESULTS: In the case eyes, the mean IOP increased along the first phase (1.8 mm Hg; p = 0.006) when compared to baseline measurements. The IOP returned to previous values after discontinuation of bimatoprost in phase 2. In the control eyes, the mean IOP did not change throughout the study. CONCLUSION: The combination of bimatoprost and latanoprost in POAG increases the IOP and should not be considered as a therapeutic option. (+info)