BACKGROUND: Although hypoxic pulmonary vasoconstriction (HPC) and hypoxic coronary vasodilatation (HCD) have been recognized by many researchers, the precise mechanism remains unknown. As isolated arteries will constrict or relax in vitro in response to hypoxia, the oxygen sensor/transduction mechanism must reside in the arterial smooth muscle, the endothelium, or both. Unfortunately, much of the current evidence is conflicting, especially concerning to the dependency of HPC and HCD on the endothelium and the role of the K+ channel. Therefore, this experiment was attempted to clarify the dependency of HPC and HCD on the endothelium and the role of the K+ channel on HPC and HCD. METHODS: HPC was investigated in isolated main pulmonary arteries precontracted with norepinephrine (NE). HCD was investigated in isolated left circumflex coronary artery precontracted with prostaglandin F2 alpha. Vascular rings were suspended for isometric tension recording in an organ chamber filled with Krebs-Henseleit solution. Hypoxia was induced by gassing the chamber with 95% N2 +5% CO2, which was maintained for 15 - 25 min. RESULTS: 1)Hypoxia elicited a vasoconstriction in NE-precontracted pulmonary arteries with endothelium, but a vasodilatation in PGF 2 alpha-precontracted coronary arteries with and without endothelium. There was no difference between the amplitude of the HPC and HCD induced by two consecutive hypoxic challenges and the effect of normoxic and hyperoxic control Krebs-Henseleit solution on subsequent response to hypoxia. 2)Inhibition of NO synthesis by the treatment with Nw-nitro-L-arginine reduced HPC in pulmonary arteries, but inhibition of the cyclooxygenase pathway by treatment with indomethacin had no effect on HPC and HCD, respectively. 3)Blockades of the TEA-sensitive K+ channel abolished HPC and HCD. 4)Apamin, a small conductance Ca2+/-activated K+ (KCa) channel blocker, and iberiotoxin, a large conductance KCa channel blocker, had no effect on the HCD. 5)Glibenclamide, an ATP-sensitive K+ (KATP) channel blocker, reduced HCD. 6)Cromakalim, an K(ATP) channel opener, relaxed the coronary artery precontracted with prostaglandin F2 alpha. The degree of relaxation by cromakalim was similar to that by hypoxia and glibenclamide reduced both hypoxia- and cromakalim-induced vasodilations. 7)Verapamil, a Ca2+ entry blocker, caffeine, a Ca2+ emptying drug; and ryanodine, an inhibitor of Ca2+ release from SR, reduced HPC, respectively. CONCLUSION: HPC is dependent on the endothelium and is considered to be induced by inhibition of the mechanisms of NO-dependent vasodilation while HCD is independent of the endothelium and is considered to be induced by activation of the K(ATP) channel.
Anoxia ; Arteries ; Caffeine ; Coronary Vessels ; Cromakalim ; Dinoprost ; Endothelium ; Glyburide ; Indomethacin ; Muscle, Smooth ; Norepinephrine ; Oxygen ; Prostaglandin-Endoperoxide Synthases ; Prostaglandins F ; Pulmonary Artery ; Relaxation ; Ryanodine ; Vasoconstriction* ; Vasodilation*

PURPOSE: To report a case of herpetic keratitis after administration of two different prostaglandin analogues. CASE SUMMARY: A 68-year-old female with a history of herpetic keratitis in her right eye after using latanoprost seven years previous presented with redness, mild ocular pain and tearing in the same eye. She had also been prescribed travoprost eye drops for both eyes for uncontrolled glaucoma one month earlier. The cornea in her right eye showed a dendritic epithelial defect with focal epithelial erosions. Travoprost treatment was discontinued, and the herpetic keratitis recovered completely in ten days with acyclovir ointment and oral agent. No further recurrence was observed in the following six months.
Acyclovir ; Aged ; Cloprostenol ; Cornea ; Eye ; Female ; Glaucoma ; Humans ; Keratitis, Herpetic ; Ophthalmic Solutions ; Prostaglandins F, Synthetic ; Prostaglandins, Synthetic ; Recurrence ; Tears ; Travoprost

PURPOSE: To evaluate the effect of dorzolamide-timolol and latanoprost on redox cycle of superoxide dismutase (SOD) and ascorbic acid in the aqueous humor of the rabbit. METHODS: Group 1 (20 eyes of 10 rabbits) was instilled with dorzolamide-timolol in the right eye and Group 2 (20 eyes of 10 rabbits) was instilled with latanoprost in the same manner. Four weeks after instillation, SOD activity and ascorbic acid concentration were analyzed. RESULTS: In Group 1, SOD activity and ascorbic acid concentration of the right eye and left eye were 15.7% and 19.3% (p=0.27), 2.7 pM and 2.6 pM (p=0.47), respectively. In Group 2, SOD activity and ascorbic acid concentration of the right and left eye were 22.3% and 27.6% (p=0.14), 2.3 pM and 2.1 pM (p=0.89), respectively. CONCLUSIONS: There was no significant difference of SOD activity and ascorbic acid concentration between both eyes in Group 1 and 2.
Aqueous Humor ; Ascorbic Acid ; Eye ; Oxidation-Reduction ; Prostaglandins F, Synthetic ; Superoxide Dismutase

PURPOSE: To analyze the clinical effectiveness of tafluprost used in the treatment of glaucoma, using ocular pulse amplitude (OPA) measurements with dynamic contour tonometry (DCT). METHODS: Sixty patients (119 eyes) with normal tension glaucoma (NTG) or primary open angle glaucoma (POAG) treated with tafluprost or other eyedrops were investigated in the present study. Intraocular pressure (IOP) was measured with Goldmann applanation tonometry (GAT), and OPA was measured with DCT, before and after treatment, retrospectively. RESULTS: In 20 patients treated with tafluprost, IOP decreased from 17.1 mm Hg before treatment to 13.0 mm Hg 3 months after treatment (24.0% descent rate), and OPA decreased from 2.35 to 1.57 (33.2% descent rate). For 20 patients who switched from another monotherapy to tafluprost, IOP decreased from 15.7 mm Hg to 13.2 mm Hg from 15.7 mm Hg (15.3%) and OPA from 2.38 to 1.69 (27.7%). CONCLUSIONS: Tafluprost used to treat glaucoma has a large OPA and IOP lowering effect and, therefore can be applied to patients who have a large OPA with glaucoma progression in spite of well controlled IOP.
Glaucoma ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Low Tension Glaucoma ; Manometry ; Ophthalmic Solutions ; Prostaglandins F

PURPOSE: To evaluate the effects of prostaglandin analogues on the corneal thickness of patients with primary open-angle glaucoma (POAG) or normal tension glaucoma (NTG). METHODS: This study included 130 eyes of 65 patients who were diagnosed with POAG or NTG. All patients were divided into two groups; one group received prostaglandin analogues, while the other group received alternative ocular hypotensive eyedrops. Corneal thickness, best corrected visual acuity, and flare in the anterior chamber were measured and compared before treatment and at least 24 months (mean: 27 months) after treatment. RESULTS: The mean decrease in corneal thickness was statistically significant in the group using prostaglandin analogues, but not in the control group. Among the various prostaglandin analogues used, travoprost and latanoprost decreased mean corneal thickness, but bimatoprost had no effect. Best corrected visual acuity, refraction power, and flare in the anterior chamber did not change significantly in either group of patients when ocular hypotensive eyedrops were used. CONCLUSIONS: Prostaglandin analogues lower intraocular pressure and decrease corneal thickness if used over a 24 months.
Amides ; Anterior Chamber ; Cloprostenol ; Eye ; Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Low Tension Glaucoma ; Ophthalmic Solutions ; Prostaglandins F, Synthetic ; Prostaglandins, Synthetic ; Visual Acuity ; Bimatoprost ; Travoprost

Bovine embryos (day 5) were cultured to day 10 with or without 100 ng/mL PGF2α in medium supplemented with control; 100 nM Dex; 1,000 U/mL recombinant human leukemia inhibitory factor (rhLIF); or Dex+rhLIF. Although the rates to development to the blastocyst were not significantly different among groups, the hatching rate after additional culture with Dex +/or rhLIF was significantly higher in all supplemented groups than the control (p < 0.05). In the presence of PGF2α, the hatching rate was significantly restored in all supplemented groups relative to the group treated with only PGF2α and the control (p < 0.05). Embryo transfer (ET) was performed with blastocysts (day 7). PGF2α levels of control recipient cows were significantly higher in the circulatory blood samples collected 60 min after ET than in samples collected 60 min before ET (p < 0.005), and were decreased in cows injected with loading medium supplemented with Dex+rhLIF (p < 0.005). Pregnancy rate was significantly higher in the ET group that received supplemented embryo-loading medium than in the non-supplemented control (p < 0.05). The intrauterine administration of Dex and rhLIF at ET prevented increased PGF2α in circulatory blood and resulted in enhanced pregnancy rate.
Animals ; Blastocyst ; Cattle* ; Dexamethasone* ; Embryo Transfer* ; Embryonic Structures* ; Fertilization in Vitro ; Humans* ; Leukemia Inhibitory Factor* ; Leukemia* ; Pregnancy Rate* ; Pregnancy* ; Prostaglandins F

The present study was conducted in order to verify the efficacy of lower doses and alternative routes of a prostaglandin F2 alpha analogue, luprostiol (PGF), for the induction of luteolysis and the precipitation of estrus in nonlactating Nelore cows (Bos taurus indicus). A conventional dose (15 mg) of PGF was compared to doses lower than the conventional dose, which ranges from 10 to 50%, that were administered intramuscularly (IM), intravulvosubmucosally (IVSM), or in the Bai-hui acupuncture site located within the lumbosacral area. The cows were administered PGF 8 day after estrus in the presence of a corpus luteum, and randomly assigned to the following groups: G1 (positive control), 15 mg, IM (n = 23); G2, 7.5 mg, IM (n = 23); G3, 3.75 mg, IM (n = 24); G4, 7.5 mg, IVSM (n = 25); G5, 3.75 mg, Bai-hui acupoint (n = 24); and G6, 1.5 mg, Bai-hui acupoint (n = 25). The results indicated that 50% of a conventional dose of PGF (7.5 mg) resulted in a complete luteal regression (plasma progesterone <1 ng/ml) at Hour 48, and hastened estrus, regardless of whether or not PGF was administered IM or IVSM. Comparatively, 10 or 25% of the conventional dose, even when administered to the Bai-hui acupoint, resulted in an initial reduction in the concentration of progesterone at Hour 24, followed by an increase observed at Hour 48. In conclusion, 25% of a conventional PGF dose administered via the Bai-hui acupoint proved inadequate to induce a complete luteal regression, whereas 50% of a conventional dose administered IM or IVSM was found to be the minimal dose required to induce effectively a complete luteal regression, and to precipitate the onset of estrus in nonlactating Nelore cows.
Acupuncture ; Animals ; Cattle/*physiology ; Dose-Response Relationship, Drug ; Female ; Injections, Intramuscular/veterinary ; Luteolysis/*drug effects ; Progesterone/blood ; Prostaglandins F, Synthetic/*administration & dosage

BACKGROUNDLatanoprost, a prostaglandin F2alpha analog, has been shown to be an effective intraocular pressure lowering agent which acts by inducing ciliary muscle cells to synthesise matrix metalloproteinases. However, the response of ciliary melanocytes to latanoprost has never been reported. This research has investigated the ability of latanoprost to induce matrix metalloproteinase-1 expression in human ciliary melanocytes, and thereby advance the understanding of the mechanism of PGF(2alpha) in decreasing intraocular pressure.

METHODSIn vitro human ciliary melanocytes were treated for 48 hours with five different concentrations of latanoprost (100, 150, 200, 500, and 1000 nmol/L). Ciliary melanocytes treated with 0.01% ethanol (vehicle) were used as a control. The expression of matrix metalloproteinase-1 in ciliary melanocytes was determined by Western blotting and immunofluorescent staining.

RESULTSWestern blotting showed that the expression of matrix metalloproteinase-1 in ciliary melanocytes was induced by latanoprost, and the level of expression was dependent on the concentration of latanoprost in the culture medium. Immunofluorescent staining showed that matrix metalloproteinase-1 was confined to the ciliary melanocyte cytoplasm.

CONCLUSIONSLatanoprost induced the expression of matrix metalloproteinase-1 in human ciliary melanocytes in a dose-dependent manner. Ciliary melanocytes, as well as ciliary muscle cells, may also play an important role in uveoscleral outflow modulation.

Cells, Cultured ; Ciliary Body ; cytology ; drug effects ; enzymology ; Female ; Fluorescent Antibody Technique ; Humans ; Immunoblotting ; Male ; Matrix Metalloproteinase 1 ; analysis ; Melanocytes ; drug effects ; enzymology ; Prostaglandins F, Synthetic ; pharmacology

The use of ophthalmic drugs and contact lens solutions has increased and allergic contact dermatitis due to these agents has also recently increased. The first case was a 67-year-old female patient who developed allergic contact dermatitis after application of Latano(R): The patch test with the ingredients in Latano(R) showed positive reaction to latanoprost and benzalkonium chloride. The second case was a 63-year-old female patient who developed allergic contact dermatitis after application of Ecolicin(R), Tolon(R), Forus(R) and Uniten-F(R): The patch test showed a positive reaction to Tolon(R). She didn't want further evaluation. The third case was a 51-year-old female patient who developed allergic contact dermatitis after application of Terramycin(R) eye ointment: the patch test with the ingredients of Terramycin(R) eye ointment showed a positive reaction to polymyxin B. When contact dermatitis occurs in periorbital areas, topical ophthalmic ointment or lens cleanser needs to be considered as a causative agent.
Aged ; Benzalkonium Compounds ; Contact Lens Solutions ; Dermatitis, Allergic Contact ; Dermatitis, Contact ; Eye ; Female ; Humans ; Middle Aged ; Patch Tests ; Polymyxin B ; Prostaglandins F, Synthetic

BACKGROUND AND OBJECTIVES: It has been reported that intracoronary radiation therapy (ICRT) using a Ho-166 coated balloon inhibits restenosis of porcine coronary arteries. However, the consequences of ICRT on coronary artery endothelial function are unknown. The aim of this study is to investigate the effects of ICRT using a Ho-166 balloon on coronary artery endothelial function and vasomotor reactivity. MATERIALS AND METHODS: Female pigs (25-35 kg) were orally premedicated daily with aspirin (100 mg) and ticlopidine (250 mg) for the duration of the study. Under sterile conditions with local anesthesia of the skin provided by 2% lidocaine, an arteriotomy of the left carotid artery was performed, an 8 Fr sheath was inserted, and intraarterial heparin sodium (10,000 IU) was injected. Under fluoroscopic guidance, the coronary artery main branch was selected through an 8 Fr guiding catheter for coronary artery overdilation injury (balloon to artery ratio, 1.3:1) and ICRT. A Ho-166 coated balloon prepared to deliver 20 Gy at a depth of 2 mm from the balloon surface was used for ICRT. The coronary artery main branch in each pig was randomly assigned to either balloon injury (Group I) or balloon injury plus ICRT (Group II). Coronary artery segments were taken from the animals at 0 week (n=8), 4 weeks (n=6) and 8 weeks (n=8) after the intervention. Data in each group denote the relative ratio compared to non-injured coronary artery and are expressed as mean +/- standard error of mean. RESULTS: The degree of KCl-induced contractile response (g) was not different between the two groups at 0 and 4 weeks, but was significantly decreased in group II compared to group I at 8 weeks (I:1.04+/-0.06, II:0.79+/-0.07, p=0.014). In rings precontracted with prostaglandin F 2alpha (PGF 2alpha), the degree of NO-dependent relaxation (%) induced with substance P was significantly decreased in group II compared to group I at 0 week (I:0.93+/-0.33, II:0.47+/-0.31, p=0.03), but the difference between the two groups was not significant at 4 and 8 weeks. In rings precontracted with PGF 2alpha and LAME in the presence of indomethacin, the degree of EDHF-induced relaxation (%) using substance P was not different between the two groups at 0, 4 and 8 weeks; nor was the degree of sodium nitroprusside-induced endothelium independent relaxation (%) in depolarized conditions with PGF 2alpha. CONCLUSION: Endothelial function of the porcine coronary artery is only transiently impaired after ICRT using a Ho-166 coated balloon. Therefore this therapy can be used as an effective method to prevent restenosis after percutaneous coronary intervention.
Anesthesia, Local ; Angioplasty ; Animals ; Arteries ; Aspirin ; Carotid Arteries ; Catheters ; Coronary Restenosis ; Coronary Vessels ; Endothelium ; Female ; Heparin ; Humans ; Indomethacin ; Lidocaine ; Percutaneous Coronary Intervention ; Prostaglandins F ; Relaxation ; Skin ; Sodium ; Substance P ; Swine ; Ticlopidine