PURPOSE: To investigate the effects of topical prostaglandin analogue drugs on the differentiation of adipocytes. METHODS: Differentiation of 3T3-L1 preadipocytes was induced with isobutylmethylxanthine, dexamethasone, and insulin. 3T3-L1 cells were exposed to 0.008, 0.08, 0.2 microM of latanoprost and travoprost. Reverse transcription polymerase chain reaction for mRNA expression of lipoprotein lipase and peroxisome proliferator-activated receptor gamma 2 (PPARgamma2), and glycerol-3-phosphate dehydrogenase (G3PDH) assays were performed to examine the effects on early and late differentiation, respectively. Also, glycerol assays were done to evaluate the effect of prostaglandin analogues on lipolysis after differentiation. RESULTS: Both prostaglandin analogues inhibited differentiation of preadipocytes. Topical prostaglandin analogues significantly decreased G3PDH activity, a marker of late differentiation. However, topical prostaglandin analogues did not change mRNA expressions of lipoprotein lipase and PPARgamma2, markers of early differentiation. The activities of the early markers of differentiation were not changed significantly before and after growth arrest. Compared to latanoprost, travoprost decreased G3PDH activity more significantly (p < 0.05). Both prostaglandin analogues did not affect the lipolysis of differentiated adipocytes (p > 0.05). CONCLUSIONS: Prostaglandin analogues display an inhibitory effect on the differentiation of adipocytes when the cells start to differentiate especially in the late stage of differentiation. Thus, commercial topical prostaglandin analogues may decrease the fat contents of eyelids.
3T3-L1 Cells ; Adipocytes/drug effects/*pathology ; Animals ; Antihypertensive Agents/administration & dosage ; Cell Differentiation/drug effects ; Disease Models, Animal ; Glaucoma/*drug therapy/pathology ; Lipolysis/*drug effects ; Mice ; Neuroprotective Agents/administration & dosage ; Ophthalmic Solutions/administration & dosage ; Prostaglandins F, Synthetic/*administration & dosage ; Prostaglandins, Synthetic/*administration & dosage

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

PURPOSE: Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin analogs with varying concentrations of benzalkonium chloride (BAC), preservative-free (PF), and alternative preservatives on mouse corneal tissue. METHODS: Thirty-five, 8- to 10-week-old female C57BL/6 mice (five mice for each group) were used for this study. To the control group, we applied normal saline, and to each drug-treated group we applied 0.02% BAC, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), travoprost 0.004% (with 0.001% polyquad) or tafluprost 0.0015% with/without 0.001% BAC, once a day (9 p.m.) for 4 weeks. Corneal fluorescein staining was evaluated in all groups. After harvest, the corneal tissues were embedded in paraffin and then Hematoxylin-Eosin stain was performed for histopathological examination. Immunofluorescence staining was done against TNF-alpha, IL-6, HLA DR, pJNK, and pAkt. RESULTS: In corneal fluorescein staining, severe punctate epithelial keratitis was seen in the groups of 0.02% BAC, 0.02% BAC containing bimatoprost 0.01% and latanoprost 0.005%. The surface desquamation, irregular surface, loss of cell borders, anisocytosis and stromal shrinkage were observed in the groups of BAC-containing eye drops. Moreover, the groups treated with BAC-containing eye drops have high inflammatory markers, significantly decreased cell viability-related signal, pAkt, and higher apoptosis-inducing signal, pJNK, than the control group. On the other hand, travoprost 0.004% and PF tafluprost 0.0015% have less cellular morphologic changes, lower inflammation, and higher cellular viability than BAC-containing formulations. CONCLUSIONS: Corneal damage, increased inflammation and apoptosis and low cell viability were observed in BAC-containing groups. PF or alternatively preserved glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
Animals ; Cell Survival ; Conjunctiva/drug effects/*pathology ; Disease Models, Animal ; Epithelium, Corneal/drug effects/*pathology ; Female ; Glaucoma/*drug therapy/pathology ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Ophthalmic Solutions ; Preservatives, Pharmaceutical ; Prostaglandins, Synthetic/*administration & dosage

Acute Disease ; Administration, Intravaginal ; Alprostadil ; adverse effects ; analogs & derivatives ; therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Middle Aged ; Myocardial Infarction ; chemically induced ; drug therapy ; Nitroglycerin ; therapeutic use ; Pessaries ; Prostaglandins E, Synthetic ; adverse effects ; therapeutic use

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

PURPOSE: To evaluate the intraocular pressure (IOP) -lowering efficacy of latanoprost in normal-tension glaucoma (NTG). METHODS: One-hundred and seventeen eyes of 63 NTG patients treated with 0.005% latanoprost once a day were enrolled in this study. Of these, 85 eyes of 47 patients were treated for 12 months. Mean IOPs were analyzed, and the mean IOP reductions from the untreated baseline were assessed after two weeks and after 1, 3, 6, 9, and 12 months of treatment. RESULTS: The mean untreated baseline IOP was 15.0+/-2.7 mmHg. After two weeks of latanoprost treatment, the mean IOP reduction from the baseline value was 2.6+/-0.2 mmHg (17.3%, p< 0.05), and after 6 and 12 months, the reduction was 2.4+/-0.2 mmHg (16.0%, p< 0.05) and 2.4+/-0.2 mmHg (16.0%, p< 0.05), respectively. Patients with a baseline IOP of > or=15 mmHg achieved significantly higher IOP reductions than those with a baseline IOP of < 15 mmHg at all follow-ups (p< 0.05). CONCLUSIONS: Latanoprost was found to be well tolerated and to significantly reduce IOP in NTG patients.
Treatment Outcome ; Time Factors ; Retrospective Studies ; Prostaglandins F, Synthetic/administration & dosage/*therapeutic use ; Middle Aged ; Male ; Intraocular Pressure/*drug effects/physiology ; Humans ; Glaucoma, Open-Angle/*drug therapy/physiopathology ; Follow-Up Studies ; Female ; Dose-Response Relationship, Drug ; Antihypertensive Agents/administration & dosage/*therapeutic use ; Aged, 80 and over ; Aged ; Adult