Additional intracervical prostaglandin reduces induction to calving time in buffaloes affected with incomplete cervical dilatation post-uterine detorsion.

Conventional induction protocol (CIP) of calving in buffaloes employs the intramuscular (IM) administration of dexamethasone (40 mg) and cloprostenol sodium (500 µg). If there is no progression in terms of cervical dilatation, then a second dose of cloprostenol sodium (500 µg) is administered intramuscularly. This protocol possesses certain demerits: (1) a wide range of response time intervals, and (2) increased risk of fetal membrane retention. Considering the cervix as a caudal continuation of the myometrium with its own contractile potential, and the limitations of CIP, we developed intracervical (IC) drug administration route in buffaloes. The proposed technique was evaluated for its use in a total of 22 cases of incomplete cervical dilatation in uterine torsion-affected buffaloes (IC-14 and IM-8). In addition to CIP, the IC group received an intracervical injection of cloprostenol sodium (500 µg) at the start of the experiment whereas the IM group received an extra intramuscular dose of cloprostenol sodium (500 µg) either after 24 h or when no progression in cervical dilatation is noticed. Surprisingly, the average response time during the experiment in the IC group was 5.8 h shorter (p < 0.000) than in the IM group (IC-5.7 ± 0.17 h vs. IM-11.9 ± 0.74 h). The duration from calving to fetal membrane expulsion (IC-12.8 ± 0.60 h vs. IM-17.5 ± 1.40 h; p < 0.002) and incidence of retention of fetal membrane were also less in the IC group (57.1% vs. 87.5%). The proposed intracervical drug administration potentiates cervical dilatation and can be regarded as a safe, effective, and feasible technique for attaining reliable results.

Bimatoprost Implant Biodegradation in the Phase 3, Randomized, 20-Month ARTEMIS Studies.

Purpose: To evaluate the time course of biodegradation of an intracameral, biodegradable, sustained-release bimatoprost implant that lowers intraocular pressure without the need for daily eye drops. Methods: In 2 identically designed, randomized, phase 3 clinical trials, adults with open-angle glaucoma or ocular hypertension and open iridocorneal angles inferiorly in the study eye were administered 10- or 15-µg bimatoprost implant (day 1 and weeks 16 and 32) or twice-daily topical timolol 0.5%. Implants were assessed on gonioscopy throughout the studies. Investigators reported whether implants were visible, estimated the size of visible implants relative to their initial size at implantation, and reported the implant location. Data for 10-µg implant placed on day 1 were pooled from both studies for analysis. Results: A total of 372 patients received the 10-µg bimatoprost implant. The degree of implant biodegradation at each follow-up time point was variable among patients. The implant frequently swelled during the initial phase of biodegradation from 6 to 28 weeks. Accelerated biodegradation occurred between 31 and 52 weeks, resulting in 82% of implants absent or ≤25% of initial size by 52 weeks. By month 20, 95% of implants had biodegraded to absent or ≤25% of initial size. The implant was predominantly located inferiorly in the iridocorneal angle. Conclusions: Bimatoprost implant biodegradation in phase 3 studies showed some degree of variability among patients. Clinically significant implant biodegradation was observed in the majority of patients by 12 months. Clinical studies are in progress to further understand implant biodegradation and the ideal timing for implant re-administration. ClinicalTrials.gov NCT02247804; ClinicalTrials.gov NCT02250651.

Trends in development and quality assessment of pharmaceutical formulations - F2α analogues in the glaucoma treatment.

The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products.

Duration of the hypotensive effect of prostaglandin analogues measured with the water drinking test in glaucoma patients.

OBJECTIVE: To measure the magnitude and duration of the hypotensive effect of two prostaglandin analogues in glaucoma patients using the water drinking test (WDT). METHODS: Patients received latanoprost or travoprost every 24 h and then every 48 h. Untreated WDT were performed at 7 am and with treatment 12, 36 and 44 h after the last dose; intraocular pressure (IOP) peak, fluctuation and the difference between peak and isolated IOP measurements at consultation times were calculated. RESULTS: Forty-one eyes of 21 patients with primary open-angle glaucoma were included; 22 eyes received latanoprost, and 19 received travoprost. Mean untreated isolated IOP was 17.20 standard deviation (S.D.) 3.73 and 16.95 S.D. 2.61 mmHg and peak pressure 22.45 S.D. 2.91 and 21.58 S.D. 3.79 mmHg, for the latanoprost and travoprost groups, respectively. With treatment, peak pressure was reduced by 22.64% and 20.29% at 12 h, 18.44% and 14.64% at 36 h and 16.17% and 14.46% at 44 h, respectively. The fluctuation without treatment was 4.36 and 5.11 mmHg, and with treatment at 12 h was reduced to 2.77 and 2.89 mmHg, increasing again at 36 and 44 h. CONCLUSIONS: A hypotensive effect was evident up to 44 h after the last dose of latanoprost and travoprost, similar for the two drugs and decreasing over time. IOP fluctuation was only reduced at 12 h.

Granulomatous uveitis and choroidal detachment in a patient after topical treatment with Bimatoprost: A case report.

BACKGROUND: Bimatoprost 0.03% is an intraocular pressure (IOP) lowering prostaglandin analog with different adverse side effects such as potential ocular inflammatory effect and ocular hyperemia. CASE PRESENTATION: We report a case of 80-year-old woman diagnosed with bilateral glaucomatous uveitis, and choroidal detachment in the left eye after topical bimatoprost administration. During the patient's hospitalization, Bimatoprost treatment was discontinued and local steroid therapy was administrated. After 1 week we reported a marked improvement of visual acuity, IOP measurement was 12 mmHg in both eyes. Anterior segment examination showed complete resolution of conjunctival and pericheratic hyperemia with significant reduction of endothelial precipitates in both eyes. CONCLUSIONS: In our case, the anterior granulomatous uveitis occurred in both pseudophakic eyes and the choroidal detachment (CD) in the eye that previously had trabeculectomy. Probably the scar tissue of the trabeculectomy allowed a better penetration of the Bimatoprost or a greater sensitivity due to an altered trabecular tissue. This work confirms that the onset physiopathology mechanism of granulomatous uveitis and CD following instillation of Bimatoprost remains uncertain.

Comparison between Latanoprost, Travoprost, and Tafluprost in reducing intraocular pressure fluctuations in patients with glaucoma.

PURPOSE: To compare the efficacies of latanoprost 0.005%, travoprost 0.004%, and tafluprost 0.0015% in reducing diurnal intraocular pressure (IOP) fluctuations in patients with newly diagnosed primary open-angle glaucoma (POAG). METHODS: In this prospective randomized clinical trial, 60 patients who were newly diagnosed with POAG were divided into three equal groups. Patients were examined at presentation and at second and sixth weeks. Diurnal phasing of IOP was conducted using a calibrated Goldmann applanation tonometer. IOP measurements were recorded from 8:00 am to 9:00 am, from 3:00 pm to 4:00 pm, and from 7:00 pm to 8:00 pm. RESULTS: The study groups were distributed similarly in terms of age and gender (p-values: 0.76) and the participants had a mean age of 52.98 ± 13.43 years. The IOP at the day of inclusion was not statistically significant among the three groups (p-values 0.27, 0.51, and 0.64 at 8 am, 2 pm, and 8 pm, respectively). Similar nonsignificant differences were noticed on the follow-up visits. However, the tafluprost group showed a significant reduction in IOP on the follow-up visit at the second week at 8 pm (30.5% reduction, p-value: 0.03). All three drugs showed a comparable and significant reduction in IOP and IOP fluctuations. The pattern of side effects was similar in all the groups. CONCLUSION: Latanoprost, travoprost, and tafluprost show a similar effectiveness in reducing the mean IOP and the diurnal IOP fluctuation in POAG. Importantly, the three drugs have comparable tolerability with insignificant differences regarding the pattern of their side effects.

Fertility outcome after medically treated pyometra in dogs.

Cystic endometrial hyperplasia-pyometra complex (CEH/P) is a challenge in canine reproduction. Present study aimed to assess fertility after medical treatment. One-hundred-seventy-four bitches affected by CEH/P received aglepristone on days 1, 2, 8, then every 7 days until blood progesterone < 1.2 ng/mL; cloprostenol was administered on days 3 to 5. Records were grouped according to bodyweight (BW): small (< 10 kg, n = 33), medium (10 ≥ BW < 25 kg, n = 44), large (25 ≥ BW < 40 kg, n = 52), and giant bitches (BW ≥ 40 kg, n = 45). Age; success rate; aglepristone treatments number; relapse, pregnancy rates; diagnosis-relapse, -first, -last litter intervals; litters number after treatment, and LS were analyzed by ANOVA. Overall age was 5.14 ± 1.75 years, without difference among groups. Treatment was 100% successful, without difference in treatments number (4.75 ± 1.18), relapse (15/174, 8.62%) and pregnancy (129/140 litters, 92.14%) rates, intervals diagnosis-relapse (409.63 ± 254.9 days) or -last litter (418.62 ± 129.03 days). The interval diagnosis-first litter was significantly shorter (163.52 ± 51.47 days) and longer (225.17 ± 90.97 days) in small and giant bitches, respectively. Overall, 1.47 ± 0.65 litters were born after treatment. Expected LS was achieved in each group, as shown by ΔLS (actual-expected LS by breed, overall -0.40 ± 1.62) without differences among groups. Concluding, CEH/P affects younger dogs than previously described. Relapses were rarer than previously reported. Medical treatment with aglepristone+cloprostenol is effective and safe, preserving subsequent fertility, as demonstrated by negligible changes in LS.

Stimulation of Bladder Acupoints by Cloprostenol for Treating Back Soreness in Athletic Horses.

Twenty-five Thoroughbred jumper geldings suffered back soreness with poor performance, and 5 control horses were assessed by archived computer data, clinical examination, and laboratory analyses of complete blood picture, serum enzymes, and cortisol level, before and after cloprostenol-pharmacopuncture. The 25 diseased horses before therapy showed significant increases in aspartate aminotransferase and creatine phosphokinase with clinical pains scored mild in 15 horses, moderate in 9 horses, and severe in one horse, without changes in the hormonal and hematological data. After therapy, they responded by an increase of heart rate (57.8 ± 4.3 bpm), body temperature (38.5 ± 0.7°C), respiration rate (28.3 ± 2.1 bpm), and capillary refilling time (CRT) (1.0 ± 0.0). On the 2nd day, a significant decrease in the mean levels of aspartate aminotransferase and creatine phosphokinase (P = 0.001) was detected, while on the 4th day, they mimed the level of the 5 controls, and on the 6th day, they showed a significant decrease (P = 0.002). The serum cortisol level showed a significant increase on the 6th day of treatment (P = 0.013). The blood picture showed significant increases in red blood cells, mean corpuscular volume, platelets, white blood cells, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean platelet volume, platelet distribution width, lymphocytes, plateletcrit, and large platelet concentration ratio (P < 0.05) and nonsignificant changes in hematocrit, granulocytes, and midocytes. The improved blood parameters, enzymes, hormones, and performance progress after cloprostenol-pharmacopuncture proved its effectiveness in treating back soreness in athletic horses.

Effect of single treatment with cloprostenol or dinoprost on estrus and reproductive performance in anestrous dairy cows after service.

Previous studies have compared the effectiveness of dinoprost and cloprostenol in cows yielding conflicting results. The aim of our study was to evaluate the efficacy of single treatment with cloprostenol or dinoprost on estrus and reproductive performance in cows with unobserved estrus after service. The study was conducted over four years in two dairy herds of Polish Holstein Frisian cows under a herd health program with an average milk yield per cow over 9000 L. Cows (n=523) diagnosed ultrasonographically as non-pregnant and with a corpus luteum were randomly assigned to be treated with either cloprostenol (n=261) or dinoprost (n=262). The estrus detection rates after administration of cloprostenol or dinoprost were 59.4%, and 57.6%, respectively. The difference between both groups was not statistically significant (p>0.05). Distribution of observed estrus did not differ between cloprostenol and dinoprost. There were no differences (p>0.05) between cloprostenol and dinoprost in conception rate (65.2% vs. 66.2%, respectively) and pregnancy rate (57.5% vs. 54.9%, respectively). Mean days open were similar in cows of both treatments (177.5 ± 74.6 days vs. 175.8 ± 62.6 days, respectively; p>0.05). In conclusion, data from this study showed no significant differences in estrus detection rates and fertility between cows with unobserved estrus after service treated with cloprostenol or dinoprost. Both products are equally useful for the treatment of non-pregnant dairy cows with anestrus after service within a reproductive herd health program.

Evaluating reproductive performance of three estrus synchronization protocols in Ghezel ewes.

Although estrus synchronization considered valuable management tools for improving reproductive performance of ewes, their high expenses and complicated usage prevent sheep farmers to apply these techniques. Therefore, the present study was designed to compare three protocols of estrus synchronization on reproductive performance of Ghezel ewes. For this reason, 27 Ghezel ewes were assigned to three estrus synchronization treatment groups based on a completely randomized design included: progestogen sponge for 12 days + 500 IU eCG at the time of sponge withdrawal (P4eCG group, expensive synchronization), two doses of 75 µg cloprostenol with 12 days interval (CLO group, economical synchronization), and CLO +500 IU eCG at day 12 (CLOeCG group, moderately priced synchronization). Four consecutive blood samples were also collected during the experiment to evaluate progesterone concentrations. The results of the present experiment showed that pregnancy and lambing rates of the first estrus as well as blood progesterone concentration were not affected by the treatments (P > 0.05), though total pregnancy and lambing rates were higher in both P4eCG and CLOeCG groups (P < 0.01). Accordingly, both P4eCG and CLOeCG protocols successfully improved reproductive traits of ewes, though CLOeCG protocol is an advisable technique for sheep farmers through its moderate price, simple application, and high reproductive performance.

Hydrometra in dairy goats: Ultrasonic variables and therapeutic protocols evaluated during the reproductive season.

Hydrometra is characterized by the accumulation of fluid within the uterus due to the persistence of corpus luteum. The diagnosis of this disorder occurs with an ultrasonic exam. This study evaluated uterine drainage and fertility rates in goats after the use of d-cloprostenol in association or not with Gonadotropin-releasing hormone (GnRH) treatment. Twenty Saanen goats, diagnosed with hydrometra, received three 37.5-µg doses of d-cloprostenol laterovulvarly at 10-day intervals. On D5, the goats were assigned into two groups receiving 1 mL of GnRH or saline solution intramuscularly. Ultrasonography (US) was performed from D0 to D25. An US approach was used to rank hydrometra in scores. The pregnancy rate was assessed 45 and 90 days after the end of treatment. The uterine fluid was totally drained after the first and second administration of d-cloprostenol in 50% and 95% of the goats, respectively. In one female, full emptying of the uterus occurred only after D20. US performed at 45 and 90 days after the end of treatment indicated there was a pregnancy rate of 45.0% and 55.0%, respectively. Fertility did not differ between the GnRH-treated and control goats. Those goats not pregnant at 45 days had a follicular cyst, hydrosalpinx or hydrometra. At 90 days, no change was observed in the hydrosalpinx, and four goats had hydrometra. The use of three doses of d-cloprostenol 10 days apart was efficient for induction of draining the contents of the uterus, resulting in a relatively acceptable pregnancy rate. This treatment associated with the US approach can be important when applied in the field.

Bilateral choroidal effusion after selective laser trabeculoplasty. / Desprendimiento coroideo seroso bilateral tras trabeculoplastia selectiva láser.

Selective laser trabeculoplasty (SLT) is an effective treatment to treat open-angle glaucoma with a low risk of complications. The case is presented of a 73 year-old woman with uncontrolled primary open-angle glaucoma who underwent selective laser trabeculoplasty in both eyes and developed bilateral choroidal effusion.

Resynchronising returns to service in anoestrous dairy cows in the South Island of New Zealand.

AIMS: To investigate the effect of targeted resynchronisation of cows treated for non-observed oestrus before the planned start of mating (PSM), that were not detected in oestrus or pregnant 23 days after treatment (phantom cows), on the proportion pregnant at 42 days after PSM and the end of mating. METHODS: Farm staff from eight herds in two regions of the South Island of New Zealand identified 1,819 cows not showing oestrus by 10 days before PSM. These cows were treated with intravaginal progesterone for 7 days, and I/M gonadorelin 10 days and 1 day before PSM. Three days before PSM they were injected with cloprostenol and equine chorionic gonadotrophin, with fixed time artificial insemination (FTAI) at PSM. By 23 days after PSM, 1,218 cows had not returned to oestrus. Of these, 161 cows confirmed not pregnant by transrectal ultrasonography were randomly assigned to no treatment (control group; n=74) or were resynchronised 25 days after PSM using the same treatment programme as above, with FTAI 35 days after PSM (n=87). All cows that returned to oestrus were artificially inseminated until 42 days after PSM, when natural mating was used. All cows were examined using transrectal ultrasonography 80 to 90 days after PSM to confirm conception dates. RESULTS: Of the 1,819 anoestrous cows treated before PSM, 526 (29 (95% CI=23.1-34.0)%) had not been observed in oestrus by 23 days after PSM and had not conceived, so were diagnosed as phantoms cows. For resynchronised cows, 42/87 (48 (95% CI=37.8-58.8)%) were pregnant by 42 days after PSM compared to 21/74 (28 (95% CI=18.1-38.7)%) control cows (p=0.009). At the end of mating 58/87 (67 (95% CI=56.6-76.7)%) cows in the resynchronised group were pregnant and 46/74 (62 (95% CI=50.9-73.2)%) in the control group (p=0.554). The hazard of conception from 21 to 42 days after PSM was 1.9 (95% CI=1.07-3.12) times greater for resynchronised than control cows (p=0.026). CONCLUSION: In cows not observed in oestrus and treated before PSM, resynchronisation increased the proportion pregnant by 42 days after PSM. CLINICAL RELEVANCE: The benefit of resynchronisation depends on the number of anoestrous cows before PSM and the number of phantom cows after PSM. However at the herd-level it is likely that providing advice to reduce the known risk factors for cows not being observed in oestrus before the PSM may well be more cost effective than identifying and treating a sub-population of phantom cows.

Fixed Combination of Travoprost and Timolol Maleate Reduces Intraocular Pressure in Japanese Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: A Prospective Multicenter Open-Label Study.

INTRODUCTION: The efficacy of lowering intraocular pressure (IOP) and safety of switching to travoprost/timolol fixed combination ophthalmic solution (Duotrav(®), Alcon Laboratories, Inc., Fort Worth, TX, USA) in patients with primary open-angle glaucoma, normal tension glaucoma or ocular hypertension undergoing prostaglandin analog (PGA) monotherapy was investigated. METHODS: Patients treated with travoprost, latanoprost, tafluprost, or bimatoprost for ≥3 months and requiring additional medication were switched to Duotrav without washout. Baseline IOP was calculated from measurements at two visits during PGA monotherapy. IOP reductions at 4, 8, and 12 weeks after switching to Duotrav and adverse events were assessed. RESULTS: Of 162 patients enrolled, 157 patients (96.9%) with ≥4 weeks of follow-up after switching to Duotrav were analyzed. The mean IOP decreased significantly (baseline = 16.3 ± 3.1 mmHg; 4 weeks = 14.6 ± 3.1 mmHg, 8 weeks = 14.7 ± 3.3 mmHg, 12 weeks = 14.6 ± 3.2 mmHg; all P < 0.0001). When study eyes were divided into three groups according to baseline IOP (≥19 mmHg: 33 eyes, 21.0%; ≥15 to <19 mmHg: 78 eyes, 49.7%; <15 mmHg: 46 eyes, 29.3%), all groups showed significant IOP reductions (P = 0.0324 ~ P < 0.0001) after switching to Duotrav. Twenty-seven of 166 patients (16.3%) in the safety analysis experienced adverse events and 26/166 patients (15.7%) experienced adverse events, for which a relationship to Duotrav could not be ruled out. Adverse events in five patients led to treatment discontinuation (eye pruritus; eye irritation; increased blood pressure and rash; increased blurred vision; deepening of the eyelid sulcus and blepharoptosis). Twelve weeks after treatment switching, eyelash changes, blepharal pigmentation and deepening of the eyelid sulcus occurred in 42 (26.8%), 29 (18.5%), and 13 (8.3%) cases, respectively, among 157 patients with follow-up. There was no significant worsening from baseline for superficial punctate keratopathy (SPK) or conjunctival hyperemia after switching (SPK score: baseline = 0.58 ± 1.31; 12 weeks = 0.92 ± 1.76, P = 0.1819; conjunctival hyperemia score: baseline = 0.41 ± 0.64; 12 weeks = 0.49 ± 0.63, P = 0.3774). CONCLUSION: Our findings confirm that switching to Duotrav(®) in PGA monotherapy patients shows IOP-lowering effect with minimal safety concerns. FUNDING: Japan Association of Health Service and Alcon Japan. Ltd. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier, UMIN000007028.

Electron microscopic aspects of the effects of certain prostaglandin analogs on mouse testes.

Prostaglandins were highlighted in the seminal plasma and then in the rest of the male and female genital tract. Prostaglandin analogs, firstly used in obstetrics and gynecology, are now widespread in both sexes, especially in the treatment of gastric and duodenal ulcers, glaucoma, etc. Therefore, we tried to highlight the effects of repeated administration of Cloprostenol and CIPG isopropyl ester (both prostaglandin F2α analogs) for the male gonad. In our experiment, we used Cloprostenol and CIPG isopropyl ester. We used three groups of white, male mice, aged 50-80 days, kept in standard laboratory conditions, which received the same feed. Each group included 12 mice. The first batch was the control group and received no substance at all. The second batch received 25 µg/kg of Cloprostenol dose per body per day, intraperitoneal administration (a single dose per day) on a daily basis for a four weeks period of time. The third batch received a 25 µg/kg CIPG isopropyl ester dose per body/day intraperitoneal administration (a single dose per day) on a daily basis for a four weeks period of time. After 7, 14 and 28 days of treatment, we sacrificed four animals in each of the batches by cutting their carotid arteries. The prostanoid analogs we used, Cloprostenol and CIPG isopropyl ester, have similar actions on male gonad in mice. These analogs induced significant changes in the evolution of the spermatogenesis and spermiogenesis. In relation to the treatment duration there were cellular changes suggesting apoptosis in different stages. With regard to spermiogenesis, the ultrastructural aspects indicate a decrease of the sperm structuring processes, especially in the acrosomal apparatus and chromatin.

Treatment of clinical endometritis in dairy cows by previously used controlled internal drug release devices.

Postpartum endometritis is considered as one of the diseases that lead to a potential profit reduction in dairy cows. The aims of the present study were to promote follicle growth by a previously used controlled internal drug release (CIDR) device and to evaluate its effect on the likelihood of recovery and the reproductive performance of clinical endometritis (CE) cows. Endometritis was diagnosed using ultrasonographic examination at 31 ± 3 (Day 0 of the experiment) days in milk, and CE cows were included in one of the three experimental groups according to the presence of a CL on their ovaries. Cows without CL on their ovaries received a reused CIDR device, which was previously used for 14 days (CIDR-14, n = 108), or PGF2α (PG-1, n = 112) on Day 0. In the third group, those with CL on their ovaries received PGF2α (PG-2, n = 107) at the same time. Ovarian structures, serum estradiol and progesterone concentrations were measured on Days 0, 7, and 14. Controlled internal drug release devices were removed, and response to treatment was evaluated in all treated cows on Day 14. Diameters of ovarian follicles were 11.61 ± 0.50, 12.46 ± 0.25, and 18.36 ± 0.60 mm on Day 7 and 11.63 ± 0.58, 14.35 ± 0.40, and 21.96 ± 0.77 mm on Day 14 in PG-1, PG-2, and CIDR-14 cows, respectively (P < 0.05). Serum estradiol concentrations were higher in CIDR-14 cows (141.17 ± 1.04 pg/mL) than in PG-1 (116.85 ± 1.05 pg/mL) and PG-2 (119.10 ± 1.05 pg/mL) cows on Day 7 (P < 0.05). Higher progesterone concentrations were observed in PG-2 cows than in PG-1 and CIDR-14 cows on Days 0, 7, and 14 (P < 0.001). The likelihood of clinical cure was 54.46%, 62.61%, and 64.81% in PG-1, PG-2, and CIDR-14 cows, respectively (P = 0.11). First-service conception risk, days to the first service, calving to conception interval, proportion of cows bred and pregnant by 120 days in milk did not differ among the treated groups (P > 0.05). The cumulative pregnancy risk was lower in PG-1 (77.67%) cows than in CIDR-14 (87.07%) and PG-2 (87.85%) cows (P = 0.02). In conclusion, reused CIDR would be contributed to the treatment of CE by promotion of follicle growth and induction of sustainable sources of endogenic estrogen secreted by the dominant follicle.

The fixed combination efficacy assessment in patients with secondary neovascular glaucoma and diabetes mellitus.

PURPOSE: To assess IOP-lowering efficacy of bimatoprost/timolol fixed combination (Ganfort®) in patients with diabetes mellitus (DM) and uncontrolled secondary neovascular glaucoma (NG). MATERIALS AND METHODS: Fifty patients (51 eyes) with uncontrolled secondary neovascular glaucoma and diabetes mellitus were enrolled in the study. All patients with an uncontrolled IOP have been proposed to switch current IOP-lowering therapy to Ganfort®. In case target IOP level was not reached filtration surgery was recommended. Ganfort® administration - once a day in the morning. RESULTS: IOP-lowering has been observed in all patients when switched to Ganfort®. Mean IOP level was almost 3-x lower versus baseline in 72.5% of patients (37 eyes). The patients achieved target IOP of 15-17 mmHg. As a result, no surgical intervention was required. Significant IOP-lowering has been observed in another group of patients (14 eyes, 27.5 %) nevertheless due to glaucoma progression, these patients are still subjected to surgical treatment. CONCLUSION: IOP-lowering fixed combination Ganfort® (Allergan) can be used in patients with secondary neovascular glaucoma and diabetes mellitus as a drug of choice to control the IOP level. Even in cases when target IOP is not achieved, Ganfort® can be administered in pre-operative period and helps to reduce postoperative complications.

Prostaglandin agonist effect on matrix metalloproteinase aqueous levels in glaucoma patients.

OBJECTIVE: To determine whether the aqueous levels of matrix metalloproteinases (MMPs) differ between patients with glaucoma treated with topical prostaglandin analogues and normal, nonglaucomatous control patients. Also, to note any difference in MMP levels between latanoprost, travoprost, and bimatoprost that might suggest a difference in efficacy or mechanism of action between these drugs. DESIGN: Prospective, observational study. PARTICIPANTS: Patients who were scheduled to undergo routine intraocular surgery (phacoemulsification or combined phacotrabeculectomy) as part of their standard clinical care were included. Eighteen eyes of 18 patients with glaucoma using any 1 prostaglandin analogue (latanoprost, travoprost, or bimatoprost) were compared with 8 normal control patients. METHODS: This was a multicentre study. Aqueous humour (0.2 mL) was aspirated at the beginning of the intraocular surgery through a clear corneal paracentesis. MMP-2 and -9 were quantified in the aqueous of all participants using enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in the levels of either MMP-2 (p = 0.216) or MMP-9 (p = 0.552) between the control patients and the patients with glaucoma on prostaglandins. There was no difference in the levels of MMP-2 or -9 between the latanoprost, travoprost, or bimatoprost groups. CONCLUSIONS: The levels of MMP-2 and -9 in aqueous of glaucomatous eyes on topical prostaglandin analogues were the same as those of normal age-matched control patients. This could reflect either a return to normal levels with efficacious treatment or a lack of difference between disease and nondisease states.

Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes.

Prostaglandin F2α analogs, commonly prescribed for glaucoma treatment, have been shown to induce side effects such as cutaneous hypertrichosis and hyperpigmentation. Therefore, these medications have theoretic applications in the treatment of alopecia and disorders of hypopigmentation. We reviewed the literature to find original studies assessing the use of prostaglandin F2α analogs in these settings. Studies and reports were analyzed in regards to androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring. Based on the results of these studies, and consideration of pathophysiologic mechanism, the most promising applications for prostaglandin F2α analogs include androgenic alopecia, chemotherapy-induced alopecia, and alopecia areata concurrently treated with corticosteroids.

Meta-analysis of randomized controlled trials comparing latanoprost with other glaucoma medications in chronic angle-closure glaucoma.

PURPOSE: To evaluate the efficacy and safety of latanoprost compared with other glaucoma medications in the treatment of chronic angle-closure glaucoma (CACG) and to provide the basis for clinical medication. METHODS: Major literature databases were searched for randomized controlled trials (RCT) involving latanoprost among patients with CACG. Primary outcome measures were absolute changes in intraocular pressure (IOP) and incidence of ocular adverse events. Statistical analyses included the calculation of standardized mean difference (SMD) and relative risk (RR). The statistical analysis was performed using STATA version 12.0 software. RESULTS: Ten RCT involving 1096 patients were included in this meta-analysis. Analysis showed that latanoprost was not significantly different from other glaucoma medications in reducing IOP (SMD = 0.29, 95% confidence interval [CI] -0.02 to 0.59, p=0.069). Further subgroup analysis revealed that latanoprost was superior compared with timolol (SMD = 0.64, 95% CI 0.46 to 0.82, p<0.001) and marginally inferior to travoprost and bimatoprost (SMD = -0.19, 95% CI -0.35 to -0.02, p = 0.026). As for conjunctival hyperemia, latanoprost caused a higher proportion than timolol (RR = 2.36, 95% CI 1.27 to 4.37, p = 0.007). However, latanoprost was associated with lower incidence of conjunctival hyperemia (RR = 0.42, 95% CI 0.30 to 0.59, p<0.001), and with fewer occurrence of other ocular side effects (excluding conjunctival hyperemia) than travoprost and bimatoprost (RR = 0.61, 95% CI 0.48 to 0.78, p<0.001). CONCLUSIONS: Travoprost and bimatoprost are superior in IOP control than latanoprost, but latanoprost is better tolerated in patients with CACG.