Immunohistochemical expression of HLA-DR in the conjunctiva of patients under topical prostaglandin analogs treatment

PURPOSE: Subclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. SUBJECTS AND METHODS: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. RESULTS: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). CONCLUSIONS: The use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used. © 2009 Lippincott Williams & Wilkins, Inc.

Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy

Purpose: To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP) had been insufficiently controlled on prostaglandin analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC). Methods: This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to oncedaily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12. Results: Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost). In the total population, mean IOP was significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001) in the prior travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1% reduction). Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12, TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the patients themselves, and for 94.7% of patients (54 of 57) by their physicians. Conclusion: When TTFC replaced PGA monotherapy in patients whose IOP had been uncontrolled, the outcome was a significant reduction in IOP and an acceptable safety and tolerability profile. Most patients and investigators preferred TTFC to prior PGA monotherapy. © 2012 Costa et al, publisher and licensee Dove Medical Press Ltd.

Timing of prostaglandin F2α treatment in an estrogen-based protocol for timed artificial insemination or timed embryo transfer in lactating dairy cows

Objectives were to investigate progesterone concentrations and fertility comparing 2 different intervals from PGF2α treatment and induced ovulation in an estrogen-based ovulation synchronization protocol for timed artificial insemination (TAI) or timed embryo transfer (TET) in lactating dairy cows. A total of 1,058 lactating Holstein cows [primiparous (n=371) and multiparous (n=687)], yielding 34.1±0.33 kg of milk/d at various days in milk were randomly assigned to receive treatment with PGF2α on either d 7 or 8 of the following protocol: d 0: 2mg of estradiol benzoate + controlled internal drug release device; d 8: controlled internal drug release device removal + 1.0mg of estradiol cypionate; d 10: TAI or d 17: TET. Only cows with a corpus luteum at d 17 received an embryo and all cows received GnRH at TET. Pregnancy diagnoses were performed by detection (transrectal ultrasonography) of an embryo on d 28 or a fetus on d 60. Fertility [pregnancy per artificial insemination (P/AI) or pregnancy per embryo transfer (P/ET)] was affected by breeding technique (AI vs. ET) and time of PGF2α treatment (d 7 vs. 8) at the 28-d pregnancy diagnosis for TAI [32.9% (238) vs. 20.6% (168)] and TET cows [47% (243) vs. 40.7% (244)] and at the 60-d pregnancy diagnosis for TAI [30% (238) vs. 19.2% (168)] and TET cows [37.9% (243) vs. 33.5% (244)]. The progesterone (P4) concentration at d 10 altered fertility in TAI cows, with higher P/AI in cows with P4 concentration <0.1 ng/mL compared with cows with P4 concentration ≥0.1 ng/mL, and in ET cows, with higher P/ET in cows with P4 concentration <0.22 ng/mL compared with cows with P4 concentration ≥0.22 ng/mL. Prostaglandin F2α treatment at d 7 increased the percentage of cows with P4 <0.1 ng/mL on d 10 [39.4 (85) vs. 23.2 (54)]. Reducing the period between PGF2α and TAI from 72 to 48h in dairy cows resulted in a clear reduction in fertility in cows bred by TAI and a subtle negative effect in cows that received TET. The earlier PGF2α treatment benefits are most likely mediated through gamete transport, fertilization, or early embryo development and a more subtle effect of earlier PGF2α treatment that may be mediated through changes in the uterine or hormonal environment that manifests itself after ET on d 7. © 2013 American Dairy Science Association.

Reproductive parameters of dairy goats submitted to estrus synchronization with prostaglandin F2α associated or not to hCG at estrous onset

O objetivo deste estudo foi avaliar a eficiência do uso de duas doses de PGF associadas ou não à administração de hCG no início do estro sobre os parâmetros reprodutivos de cabras leiteiras. Um total de 29 cabras receberam duas doses de 30 µg d-cloprostenol pela via latero-vulvar com 10 dias de intervalo (Dia 1 e Dia 10). As cabras foram alocadas para receberem o hCG (250 IU) ou salina i.m. no momento em que o estro foi detectado. Depois da realização da segunda dose de PGF, o estro foi monitorado e exames ultrassonográficos foram realizados duas vezes ao dia. Todas as fêmeas foram inseminadas 16 h após o inicio do estro. Amostras de sangue foram coletadas diariamente para determinação das concentrações plasmáticas de progesterona. O uso do hCG no momento do início do estro não afetou os parâmetros estudados e, portanto, os dados serão apresentados agrupados. A taxa de manifestação de estro foi similar (P > 0,05) na primeira (75,9% - 22/29) ou na segunda dose de PGF (79,3% - 23/29). O intervalo entre a administração de PGF e o início do estro foi maior (P < 0,05) no Dia 1 (75,8±53,9 h) que no Dia 10 (47,7±10,1 h). Duração do estro também diferiu (P < 0,05) 35,4±15,9 (Dia 1) vs 26,8±15, 0 h (Dia 10). A taxa de ovulação foi 79,3% (23/29) após a segunda dose PGF. Não foi encontrada diferença (P>0,05) entre os grupos experimentais quanto aos parâmetros reprodutivos: intervalo entre a aplicação da segunda dose e a ovulação (86,6±11,4h), intervalo do estro a ocorrência da ovulação (39,9±12,3h), diâmetro do maior folículo (7,2±1,4) e número de ovulações (1,8±0,6). No Dia 1, 52,4% (11/21) apresentavam concentrações de progesterona < 1 ng/mL. No Dia 10, 100% dos animais apresentavam concentrações >1ng/mL. O presente estudo permite concluir que o estro pode ser eficientemente sincronizado em cabras leiteiras com duas doses de PGF intervaladas em 10 dias. Novas pesquisas devem se realizadas para avaliar diferentes doses e momentos de utilização do hCG.

Intraocular pressure, specular microscopy, and prostaglandin E-2 concentration in dogs with mature and hypermature cataract

This study aimed to evaluate and correlate intraocular pressure (IOP), endothelial cell density (CD), and hexagonality (HEX), and the aqueous humor prostaglandin E-2 (PGE(2)) concentration in dogs with mature (MG, n = 8) and hypermature (HG, n = 8) cataracts. Eight laboratory beagles with no ocular abnormalities were included as a control group (CG). The IOP was measured using a digital applanation tonometer. Noncontact specular microscopy was used to evaluate CD and HEX. Samples of aqueous humor were used to determine prostaglandin E-2 concentration using enzyme-linked immunoassay. Data were compared by ANOVA and Bonferroni's multiple comparison test, and possible correlations among the PGE(2) aqueous concentration and corneal endothelium cell parameters were assessed by Person's test (P < 0.05). Average values of IOP (P = 0.45) and CD (P = 0.39) were not significantly different between MG, HM, and CG. Average values of HEX were lower, and PGE(2) concentration was increased in the MG and HG in comparison with CG (P < 0.05); however, such parameters did not change significantly between MG and HG (P > 0.05). PGE(2) values did not correlate with IOP, CD, and HEX in any group (P > 0.05). Although there were a small number of dogs studied, our results demonstrated that cataract progression from mature to hypermature did not have a significant change in PGE(2) aqueous concentration, IOP, corneal endothelial cell count, or morphology. In addition, PGE(2) concentration was not correlated with parameters of the corneal endothelium or IOP in dogs with mature or hypermature cataracts.

Values of 13,14-Dihydro-15-Keto-PGF(2 alpha), Progesterone and Oestradiol After Injection of Prostaglandin at Different Periods of Buffalo Puerperium

Knowledge of the effectiveness of prostaglandins in uterine involution process led to the development of protocols with its analogues in postpartum period. However, this hormone mechanism of action is not yet fully elucidated. Thus, the objective of this study was to verify if chloprostenol administration, at early or intermediary puerperium, can induce changes on progesterone, PGFM and oestradiol plasma concentrations. 30 Murrah postpartum buffaloes were randomly divided into three groups: CONT (saline, n = 10); CLO2 (chloprostenol at days 2 and 5 postpartum, n = 10) and; CLO15 (chloprostenol at days 15 and 20 postpartum, n = 10). Blood samples were collected from jugular vein to measure progesterone, PGFM and oestradiol plasma concentrations at days 2, 7, 14, 21 and 28 postpartum. CLO2 group presented lower progesterone and PGFM plasma concentrations in relation to CONT and CLO15 groups (0.23 +/- 0.00 and 0.32 +/- 0.11, 0.19 +/- 0.00 and 0.23 +/- 0.11, 0.23 +/- 0.00 and 0.30 +/- 0.19, for groups CONT, CLO2 and CLO15, respectively; P < 0.05). There was no significant difference in oestradiol plasma concentration between experimental groups (P > 0.05). Prostaglandin synthetic analogue administration induced hormonal changes in postpartum buffaloes, which can partially explain its positive effect under reproductive function of this specie.

Uterine Involution, Fluid Accumulation and Ovarian Activity after Injection of Prostaglandin at Different Periods of Buffalo Puerperium

This study aimed to evaluate the effect of chloprostenol administration, at early or intermediary puerperium, under uterine involution, intrauterine fluid accumulation and ovarian activity return. 30 Murrah postpartum buffaloes were randomly divided into three groups: CONT (saline, n = 10); CLO2 (chloprostenol at days 2 and 5 postpartum, n = 10) and; CLO15 (chloprostenol at days 15 and 20 postpartum, n = 10). Gynecological exams were performed at days 2, 7, 14, 21 and 28 postpartum, when uterine involution degree (1 to 3 scale, by transrectal palpation), intrauterine fluid accumulation (0 to 3 scale, by ultrasound exam) and ovarian activity (B-mode ultrasound exam) were evaluated. CLO2 group presented higher uterine involution (2.00 +/- 0.23, 1.66 +/- 0.23, 1.58 +/- 0.23 for groups CLO2, CONT and CLO15, respectively) and faster ovarian activity return in relation to groups CONT and CLO15 (P < 0.05). Groups CLO2 and CLO15 showed lower intrauterine fluid accumulation compared to CONT group (2.04 +/- 0.20, 1.58 +/- 0.20, 1.92 +/- 0.20 for groups CONT, CLO2 and CLO15, respectively; P < 0.05). Prostaglandin analogue administration in postpartum buffalo benefited uterine involution, lochia expulsion and ovarian activity return, improving reproductive efficiency in this specie.

Prostaglandin treatment at the onset of norgestomet and estradiol-based synchronization protocols did not alter the ovarian follicular dynamics or pregnancy per timed artificial insemination in cyclic Bos indicus heifers

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Temporal analysis of prostaglandin F2 alpha receptor, caspase 3, and cyclooxygenase 2 messenger RNA expression and prostaglandin F2 alpha receptor and cyclooxygenase 2 protein expression in endometrial tissue from multiparous Nelore (Bos taurus indicus) cows treated with cloprostenol sodium during puerperium

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of adding a gonadotropin-releasing-hormone treatment at the beginning and a second prostaglandin F-2 alpha treatment at the end of an estradiol-based protocol for timed artificial insemination in lactating dairy cows during cool or hot seasons of the year

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Luteal changes after treatment with sub-luteolytic doses of prostaglandin (cloprostenol sodium) in cattle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E-2-mediated M2 generation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of receptors for ovarian steroids and prostaglandin E2 in the endometrium and myometrium of mares during estrus, diestrus and early pregnancy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Induction of luteolysis in mares utilizing a micro-dose of prostaglandin F-2 alpha in the sacral lumbar space

An experiment was conducted to examine the luteolytic effectiveness of using low or micro doses of PGF2α when administered at the BAI HUI acupuncture point, which is frequently used to treat ovarian disturbances in veterinary acupuncture. The results indicate that PGF2α given at a very low micro dose of 0.5 mg (one tenth the conventional recommended dose) administered at the BAI HUI acupuncture point located at the sacral lumbar space is equally effective at inducing luteolysis in mid-luteal phase mares as conventional PGF2α i.m. treatment using a tenfold higher dose. Therefore, based on the results of the present study, we suggest that the BAI HUI sacrai lumbar route somehow provides an extremely efficient pathway for the drug to the ovarian level.

Reproductive parameters of dairy goats submitted to estrus synchronization with prostaglandin F2a associated or not to hCG at estrous onset

Coodernação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES)