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The Journal of Veterinary Medical... May 2022Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are...
Although feline idiopathic cystitis (FIC) distresses of many cats, its pathogenesis is unknown and the diagnosis is challenging. Polyunsaturated fatty acids (PUFAs) are metabolized into various lipid mediators. Lipid mediators such as prostaglandins (PGs) modulate inflammation and many of them are excreted into the urine. Thus, the investigation of the urinary lipid profile may reveal pathogenesis and help diagnosis of FIC. We collected urine samples from five FIC cats by spontaneous urination and analyzed 158 types of lipid mediators in urines using liquid chromatography-mass spectrometry. The urinary levels of PUFAs were higher in FIC compared to those of the healthy group. The excretions of a major inflammatory mediator, PGD, were less in FIC. Other well-known inflammatory mediators such as PGE, PGI, and their metabolites did not show a difference. In contrast, the levels of PGF and its 2 metabolites and PGF were higher in FIC. These results may provide new insights into the future management of cat FIC.
Topics: Animals; Cat Diseases; Cats; Chromatography, Liquid; Cystitis; Lipids; Mass Spectrometry; Prostaglandins F
PubMed: 35387958
DOI: 10.1292/jvms.22-0049 -
BMC Ophthalmology Apr 2017The aim of this work is to evaluate efficacy and tolerability of preservative containing 0.0015% tafluprost and preservative-free 0.0015% tafluprost using a prospective... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this work is to evaluate efficacy and tolerability of preservative containing 0.0015% tafluprost and preservative-free 0.0015% tafluprost using a prospective crossover study.
METHODS
Primary open angle glaucoma (POAG) and normotensive glaucoma (NTG) patients were randomized enrolled. Group 1 ("NPT to PT") patients used preservative-free 0.0015% tafluprost (NPT) for 6 months and then changed to preservative containing 0.0015% tafluprost(PT) for 6 months. Group 2 ("PT to NPT") patients used preservative containing 0.0015% tafluprost for 6 months and changed to preservative-free 0.0015% tafluprost for 6 months. At 1, 3, 6, 7, 9, and 12 months, we measured intraocular pressure for efficacy and graded corneal erosion, tear break-up time (TBUT), and subjective discomfort.
RESULTS
A total of 20 patients and 20 eyes were enrolled. In Group 1 and 2, intraocular pressure was well controlled to approximately 14 mmHg (9.38-18.46% decrease). Generally, subjective satisfaction was improved after changing from PT to NPT (p = 0.03) and TBUT using PT was numerically inferior to that using NPT (p = 0.06) but not when changing from NPT to PT.
CONCLUSION
Both preservative containing and preservative-free 0.0015% tafluprost reduced intraocular pressure significantly. In addition, changing medication from PT to NPT might improve subjective satisfaction and tear break up time.
TRIAL REGISTRATION
The trial registration number is NCT 03104621 (Apr/1/2017). Retrospectively registered.
Topics: Cross-Over Studies; Dose-Response Relationship, Drug; Drug Tolerance; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Tonometry, Ocular; Treatment Outcome
PubMed: 28454526
DOI: 10.1186/s12886-017-0453-z -
British Journal of Pharmacology Apr 2019Topical ophthalmic formulations of analogues of the endogenous arachidonic acid cyclooxygenase metabolite, PGF , are the standard of care treatment for the blinding... (Review)
Review
Topical ophthalmic formulations of analogues of the endogenous arachidonic acid cyclooxygenase metabolite, PGF , are the standard of care treatment for the blinding disease glaucoma. These are the most potent and efficacious medical therapies for lowering intraocular pressure (IOP), the most important risk factor identified for disease progression. They have few side effects and offer the convenience of once-a-day dosing. It was initially believed that endogenous PGs raised IOP and caused substantial ocular surface adverse effects. However, carefully designed experiments demonstrated that esterification of the carboxylic acid afforded potent and efficacious topical ocular hypotensive activity. The final hurdle to be overcome was improvement of the side effect profile. A hypothesis was advanced that the IOP-lowering effect of PGF isopropyl ester was due to activation of its cognate PG-FP receptor, while side effects were largely due to promiscuous interaction with other PG receptors. This hypothesis was validated by modification of the ω chain (carbons 13-20) to a phenyl group. This provided the first marketed FP-class PG agonist analogue (FP-PGA) ocular hypotensive agent, latanoprost. Since the introduction of latanoprost into clinical medicine to lower and control IOP, a number of additional FP-PGAs have been discovered, characterized and marketed, including travoprost, tafluprost, unoprostone isopropyl ester and bimatoprost (an amide). LINKED ARTICLES: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.
Topics: Animals; Antihypertensive Agents; Bimatoprost; Drug Discovery; Glaucoma; Humans; Prostaglandins; Prostaglandins F; Travoprost; Treatment Outcome
PubMed: 29665040
DOI: 10.1111/bph.14327 -
Indian Journal of Ophthalmology Dec 2023To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.
OBJECTIVE
To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.
METHODS
This is a retrospective chart review of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) attending regular outpatient visits in December 2019 and January 2021, and treated with topical preserved tafluprost 0.0015%. Based on their medication history, patients were divided into two groups, the "treatment naïve" group and the "switched" group, which included patients switched to tafluprost monotherapy after treatment with at least one prior drug.
RESULTS
The mean IOP of the study population reduced significantly from baseline level by 20.6% and 25.5% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with only OHT reduced significantly from baseline level by 21% and 26% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with POAG reduced significantly from baseline level by 19% and 24% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG treatment naïve patients was 25.3 ± 0.3 mmHg, which reduced significantly by 24% and 28% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG switched patients was 24.3 ± 0.1 mmHg, which reduced significantly by 18% and 22% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). In the POAG switch group, the percent reduction in IOP at 3 months after preserved tafluprost 0.0015% treatment was 23% with timolol as first line, 22% with bimatoprost as first line, 20% with latanoprost as first line, and 19% with travoprost as first line (P < 0.001 for all).
CONCLUSIONS
We show significant IOP reduction with preserved tafluprost 0.0015% in a real-world setting. As first-line monotherapy in patients with OHT and in POAG-naïve patients, preserved tafluprost 0.0015% significantly reduced IOP at 3 months. Even as second-line therapy in nonresponders (POAG-Switched) to various drugs (same class [PGAs] versus different class), treatment with preserved tafluprost 0.0015% resulted in significant IOP reduction at 3 months.
Topics: Humans; Intraocular Pressure; Glaucoma, Open-Angle; Retrospective Studies; Prostaglandins F; Ocular Hypertension; Glaucoma; Timolol; Antihypertensive Agents; Treatment Outcome
PubMed: 37991299
DOI: 10.4103/IJO.IJO_3312_22 -
Journal of Dairy Science Dec 1983Fertilization failure, mostly due to absence of sperm in the oviducts, is a major cause of reproductive inefficiency of farm animals. Sperm may be transported to the... (Review)
Review
Fertilization failure, mostly due to absence of sperm in the oviducts, is a major cause of reproductive inefficiency of farm animals. Sperm may be transported to the oviducts of cattle and sheep within a few minutes after mating or insemination, but these sperm probably fertilize few ova. Slower transport, with establishment of sperm populations in each segment of the reproductive tract, requires a few to several hours. In swine, sperm capable of fertilizing ova reach the oviducts in less than 1 h. Smooth muscle contractions of the reproductive tract, ciliary beats, fluid currents, and flagellar activity of sperm are primary mechanisms of sperm transport. Sperm become hyperactive in the oviducts in association with capacitation. Most sperm in an inseminate drain from the female reproductive tract within a few minutes or hours after insemination; remaining sperm are removed from the tract by slower drainage or phagocytosis. Sperm survival and transport in estrous ewes is reduced drastically by pastures with high estrogen content and by regulating estrus with progestogen or prostaglandin F2 alpha. The cervix is the initial site of inhibition of sperm transport in ewes, and endocrine imbalances probably are the basis of inhibition. Sperm transport problems generally are associated with immobilization and death of sperm in the uterus and anterior segments of the cervix within 2 h after mating. After gilts are inseminated with frozen-thawed semen, relatively few sperm are retained in the reproductive tract, apparently accounting for lowered fertilization rates. Sperm transport has been improved by adding to semen or administering to females such compounds as prostaglandin F2 alpha, oxytocin, estradiol, phenylephrine, or ergonovine. Estradiol, prostaglandin F2 alpha, phenylephrine, and ergonovine administered to rabbits at insemination each increased fertilization rates.
Topics: Animals; Animals, Domestic; Cattle; Dinoprost; Ergonovine; Estradiol; Fallopian Tubes; Female; Insemination, Artificial; Male; Phenylephrine; Prostaglandins F; Rabbits; Sheep; Sperm Motility; Sperm Transport; Spermatozoa; Swine; Uterine Contraction; Uterus
PubMed: 6365994
DOI: 10.3168/jds.S0022-0302(83)82138-9 -
PLoS Genetics 2013The mechanisms that guide motile sperm through the female reproductive tract to oocytes are not well understood. We have shown that Caenorhabditis elegans oocytes...
The mechanisms that guide motile sperm through the female reproductive tract to oocytes are not well understood. We have shown that Caenorhabditis elegans oocytes synthesize sperm guiding F-series prostaglandins from polyunsaturated fatty acid (PUFA) precursors provided in yolk lipoprotein complexes. Here we use genetics and electrospray ionization tandem mass spectrometry to partially delineate F-series prostaglandin metabolism pathways. We show that omega-6 and omega-3 PUFAs, including arachidonic and eicosapentaenoic acids, are converted into more than 10 structurally related F-series prostaglandins, which function collectively and largely redundantly to promote sperm guidance. Disruption of omega-3 PUFA synthesis triggers compensatory up-regulation of prostaglandins derived from omega-6 PUFAs. C. elegans F-series prostaglandin synthesis involves biochemical mechanisms distinct from those in mammalian cyclooxygenase-dependent pathways, yet PGF(2α) stereoisomers are still synthesized. A comparison of F-series prostaglandins in C. elegans and mouse tissues reveals shared features. Finally, we show that a conserved cytochrome P450 enzyme, whose human homolog is implicated in Bietti's Crystalline Dystrophy, negatively regulates prostaglandin synthesis. These results support the model that multiple cyclooxygenase-independent prostaglandins function together to promote sperm motility important for fertilization. This cyclooxygenase-independent pathway for F-series synthesis may be conserved.
Topics: Animals; Arachidonic Acids; Caenorhabditis elegans; Cytochrome P-450 Enzyme System; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Male; Mice; Oocytes; Prostaglandins F; Reproduction; Sperm Motility; Spermatozoa
PubMed: 23382703
DOI: 10.1371/journal.pgen.1003271 -
British Journal of Pharmacology Dec 19771 High-speed cytoplasmic supernatants of rat, rabbit, pig and guinea-pig kidneys were prepared and the metabolism of 10 mug/ml prostaglandin F(2alpha) labelled with...
1 High-speed cytoplasmic supernatants of rat, rabbit, pig and guinea-pig kidneys were prepared and the metabolism of 10 mug/ml prostaglandin F(2alpha) labelled with [(3)H(1)-9beta]-prostaglandin F(2alpha) studied by thin layer radiochromatography and bioassay.2 The metabolism of prostaglandin F(2alpha) measured by radiochromatography parallels biological inactivation in all species except the rabbit.3 Kidneys metabolize prostaglandin F(2alpha) by two divergent pathways, yielding a mixture of prostaglandin E and F metabolites.4 15-Hydroxyprostaglandin dehydrogenase and prostaglandin Delta-13 reductase are present in all species in characteristic proportions. Thus prostaglandin F(2alpha) is metabolized sequentially to 15-keto prostaglandin F(2alpha) and 13,14-dihydro-15-keto prostaglandin F(2alpha). The rate and profile of formation of these metabolites is species-dependent.5 13,14-Dihydro-15-keto prostaglandin F(2alpha) is the principal prostaglandin F series metabolite in all species.6 Pig and guinea-pig kidney contain an unidentified enzyme which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro prostaglandin F(2alpha).7 Rat kidney contains a high concentration of a prostaglandin 9-hydroxy dehydrogenase which converts 13,14-dihydro-15-keto prostaglandin F(2alpha) to 13,14-dihydro-15-keto prostaglandin E(2).8 Rabbit kidney contains a novel 9-hydroxydehydrogenase which oxidises prostaglandin F(2alpha) directly to E(2), thus producing a compound with more potent renal actions. The possible implications of this enzyme for kidney homeostasis are discussed.
Topics: Animals; Guinea Pigs; Kidney; Male; Prostaglandins F; Rabbits; Rats; Species Specificity; Swine
PubMed: 597667
DOI: 10.1111/j.1476-5381.1977.tb07555.x -
The British Journal of Ophthalmology Apr 1985Vitreous samples were obtained from 41 eyes undergoing vitrectomy, and radioimmunoassays were performed to measure concentrations of the prostaglandins PGE2, PGF2 alpha,...
Vitreous samples were obtained from 41 eyes undergoing vitrectomy, and radioimmunoassays were performed to measure concentrations of the prostaglandins PGE2, PGF2 alpha, prostacyclin, and thromboxane. Presumably physiological levels (approximately 100 picograms/ml) were found in vitreous from eyes undergoing cataract extraction. Eyes with vitreous haemorrhage, retinal detachment, or cystoid macular oedema had similarly low levels. Vitreous prostaglandins were mildly elevated in trauma and endophthalmitis and markedly elevated in aphakic bullous keratopathy. The role prostaglandins may play in cystoid macular oedema is reviewed.
Topics: Adult; Aged; Cataract; Dinoprost; Dinoprostone; Female; Humans; Macular Edema; Male; Middle Aged; Prostaglandins; Prostaglandins E; Prostaglandins F; Retinal Detachment; Thromboxanes; Vitreous Body
PubMed: 3857940
DOI: 10.1136/bjo.69.4.275 -
Advances in Therapy Dec 2014The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of... (Randomized Controlled Trial)
Randomized Controlled Trial
A 6-month study comparing efficacy, safety, and tolerability of the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% versus each of its individual preservative-free components.
INTRODUCTION
The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months.
METHODS
A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m.
RESULTS
In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55 mmHg (32%) for FC and -7.35 mmHg (28%) for TIM. The model-based treatment difference (FC-TIM) was -0.885 mmHg [95% confidence interval (CI) -1.745 to -0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61 mmHg (33%) for FC and -7.23 mmHg (28%) for TAF. The model-based treatment difference (FC-TAF) was -1.516 mmHg (95% CI -2.044 to -0.988; p < 0.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8% versus 6.4%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1% versus 0.0%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4%).
CONCLUSION
The preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015% and timolol 0.5% when given as monotherapies. Overall, the study treatments were safe and well tolerated.
FUNDING
Santen Oy, Tampere, Finland.
Topics: Adult; Antihypertensive Agents; Double-Blind Method; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Timolol; Tonometry, Ocular; Treatment Outcome
PubMed: 25447269
DOI: 10.1007/s12325-014-0163-3 -
Advances in Therapy Sep 2014A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a... (Review)
Review
A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.
Topics: Adrenergic beta-Antagonists; Amides; Cloprostenol; Double-Blind Method; Drug Combinations; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Randomized Controlled Trials as Topic; Timolol
PubMed: 25213118
DOI: 10.1007/s12325-014-0151-7