GnRH analogs induce a LH peak and increase pregnancy per timed-AI in ewes.

To date, there have been no studies testing the capacity of GnRH analogs and respective doses to induce a LH peak in sheep. In this sense, the present study aimed to evaluate the capacity of different synthetic forms and doses of GnRH in inducing LH release in sheep, and the effect of GnRH administration at timed artificial insemination (TAI) on pregnancy per timed-AI. In experiment 1, ewes (n = 40) received an intravaginal device (IVD) of medroxyprogesterone acetate (MPA; 60 mg) for 7 d and prostaglandin F2α analog on Day 5. On Day 7, the ewes were allocated randomly into one of eight groups (n = 5/group), which received a GnRH analog at a specific dose, as follows: lecirelin (12.5 or 25 µg), gonadorelin (50 or 100 µg), buserelin acetate (4.2 or 8.4 µg), or deslorelin (375 or 750 µg). Blood samples for LH determination were obtained at 0, 2, 4, and 6 h after GnRH and the IVDs were removed after the last blood collection. The maximal LH concentration induced by gonadorelin at doses of 50 µg and 100 µg (12.0 ± 2.4 ng/mL and 28.6 ± 7.1 ng/mL, respectively) was lower (P < 0.05) than serum LH induced by 8.4 µg of buserelin (78.9 ± 12.9 ng/mL), 375 µg and 750 µg of deslorelin (75.6 ± 7.4 ng/mL and 72.1 ± 10.6 ng/mL, respectively) and 12.5 µg and 25 µg of lecirelin (73.3 ± 17.8 ng/mL and 61.6 ± 5.9 ng/mL, respectively). However, the maximal LH concentration induced by 4.2 µg of buserelin (49.4 ± 5.9 ng/mL) was similar (P > 0.05) to the 100 µg of gonadorelin. The total release of LH (area under the curve - AUC) after treatment with 50 µg of gonadorelin (31.7 ± 5.9 ng h/mL) was lower (P < 0.05) than after other agonists. In a second experiment, 330 ewes were treated with IVD containing MPA for 7 d. Simultaneously with IVD removal, 250 µg of cloprostenol and 200 IU of eCG were administered. Then, ewes were assigned randomly to either no further treatment (control); or to receive 4.2 µg of buserelin acetate (GnRH group) at cervical TAI, which was performed with fresh semen 54 h after IVD withdrawal in all the animals. Higher pregnancy per timed-AI was observed for GnRH (50.3 %) compared to control (40.7 %). We conclude that buserelin acetate (8.4 µg), lecirelin (12.5 and 25 µg) and deslorelin (375 and 750 µg) induced a greater stimulatory effect on LH secretion than gonadorelin treatment. Furthermore, buserelin acetate treatment at TAI increased pregnancy per timed-AI in ewes previously treated with MPA and eCG.

Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits.

PURPOSE: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. METHODS: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. RESULTS: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. CONCLUSION: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits / Efeitos dos análogos da prostaglandina na velocidade do fluxo sanguíneo e resistência na artéria oftálmica de coelhos

ABSTRACT Purpose: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. Methods: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. Results: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. Conclusion: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

RESUMO Objetivo: O objetivo deste estudo foi investigar os efeitos dos análogos da prostaglandina (PGAs) no fluxo sanguíneo da artéria oftálmica em coelhos. Métodos: Cinquenta e cinco coelhos da raça Nova Zelândia clinicamente saudáveis foram divididos em seis grupos para tratamento com formulação tópica de diferentes APGs (bimatoprosta BAK, tafluprosta BAK-free, travoprosta BAK, travoprosta POLYQUAD e latanoprosta BAK) e formulações contendo apenas o conservante cloreto de benzalcônio (BAK). Foi realizada ultrassonografia com Doppler antes e após os tratamentos. Os valores do pico da velocidade sistólica (PSV) e da velocidade diastólica final foram obtidos e o índice de resistência (RI) foi então calculado. A análise estatística foi realizada para comparar as diferenças entre cada droga no pré e pós-tratamento, além das diferenças no pós-tratamento entre as drogas. Resultados: Estes colírios PGAs não afetaram o PSV. A bimatoprosta com o conservante BAK, travoprosta com o conservante POLYQUAD e latanoprosta com o conservante BAK não alteraram o RI. Já o tratamento com tafluprosta sem conservante (BAK-free) e travoprosta com o conservante BAK promoveram redução similar dos valores do RI. Não houve diferença significativa na comparação entre valores pré e pós-tratamento quando BAK foi administrado isoladamente. Conclusão: Os PGAs tafluprosta BAK-free e travoprosta BAK melhoraram o fluxo sanguíneo na artéria oftálmica em coelhos da raça Nova Zelândia sugerindo que estes medicamentos possam contribuir na prevenção da progressão do glaucoma.

Eyelash growth induced by topical prostaglandin analogues, bimatoprost, tafluprost, travoprost, and latanoprost in rabbits.

PURPOSE: Prostaglandin analogues (PGA) are ocular hypotensive agents used for the treatment of glaucoma. Hypertrichosis of the eyelashes has been reported in humans as a side effect. Eyelash growth was investigated with clinical trials in people using bimatoprost. Scattered reports of eyelash growth during the treatment of glaucoma with other PGA are also found in the literature. We investigated the effect of 4 different topical PGA on eyelash length. METHODS: Forty New Zealand white rabbits were divided into 4 groups and received daily topical application of bimatoprost, tafluprost, travoprost, and latanoprost in the left eye for 4 weeks. The right eye received no treatment. Eyelash length was measured in both eyes before and after treatment using a stainless steel digital caliper. RESULTS: Bimatoprost and tafluprost groups had significant increases in eyelash length. We did not observe significant eyelash growth in rabbits receiving travoprost and latanoprost after 1 month of treatment. CONCLUSIONS: Today, only bimatoprost is approved for growing eyelashes, and our research shows that tafluprost could be further explored by the cosmetic and pharmaceutical industry. Additional research using travoprost and latanoprost as agents for eyelash growth should be performed in the future using prolonged treatment periods to determine whether or not these PGA induce eyelash growth, and investigate other possible side effects.

The administration of exogenous prostaglandin may improve ovulation in pacu (Piaractus mesopotamicus).

Based on the reports of unsuccessful ovulation in pacu (Piaractus mesopotamicus) by fish farmers and researchers undertaking artificial reproduction programs, we evaluated the use of prostaglandin F (PGF) to improve pacu ovulation. This study was conducted during two spawning seasons (2009/2010 and 2010/2011) with two samplings in the first season and one sampling in the second season. A total of 45 females was sampled in this study. The control group was injected with carp pituitary extract (crude extract, 6 mg/kg), and the treatment group received PGF (2 mL per fish in the 2009/2010 season and 5 mL per fish in the 2010/2011 season) in addition to the crude extract. In both seasons, 100% (N = 4, 2009/2010 first sampling; N = 5, 2009/2010 second sampling; and N = 3, 2010/2011) of the PGF-treated fish spawned. In contrast, 53.0% (N = 9) and 83.3% (N = 10) of the control fish spawned in the first and second samplings of the 2009/2010 season, respectively, and only 25.0% (N = 1) spawned in the 2010/2011 season. Fecundity, fertility, and hatching rates did not differ (P > 0.05) between the treated and control fish. Based on oocyte volume frequency analysis, ovaries of the control fish had more (P < 0.05) vitellogenic oocytes with germinal vesicle breakdown that remained unovulated after spawning, whereas more (P < 0.05) of previtellogenic oocytes were present in the ovaries of the PGF-treated fish. In conclusion, administration of exogenous prostaglandin may improve the outcome of hormonally induced spawning in tropical migratory fish.

Neither plasma progesterone concentrations nor exogenous eCG affects rates of ovulation or pregnancy in fixed-time artificial insemination (FTAI) protocols for puberal Nellore heifers.

The objective was to evaluate the effects of plasma progesterone (P4) concentrations and exogenous eCG on ovulation and pregnancy rates of pubertal Nellore heifers in fixed-time artificial insemination (FTAI) protocols. In Experiment 1 (Exp. 1), on Day 0 (7 d after ovulation), heifers (n = 15) were given 2 mg of estradiol benzoate (EB) im and randomly allocated to receive: an intravaginal progesterone-releasing device containing 0.558 g of P4 (group 0.5G, n = 4); an intravaginal device containing 1 g of P4 (group 1G, n = 4); 0.558 g of P4 and PGF(2α) (PGF; 150 µg d-cloprostenol, group 0.5G/PGF, n = 4); or 1 g of P4 and PGF (group 1G/PGF, n = 3). On Day 8, PGF was given to all heifers and intravaginal devices removed; 24 h later (Day 9), all heifers were given 1 mg EB im. In Exp. 2, pubertal Nellore heifers (n = 292) were treated as in Exp. 1, with FTAI on Day 10 (30 to 36 h after EB). In Exp. 3, pubertal heifers (n = 459) received the treatments described for groups 0.5G/PGF and 1G/PGF and were also given 300 IU of eCG im (groups 0.5G/PGF/eCG and 1G/PGF/eCG) at device removal (Day 8). In Exp. 1, plasma P4 concentrations were significantly higher in heifers that received 1.0 vs 0.588 g P4, and were significantly lower in heifers that received PGF on Day 0. In Exp. 2 and 3, there were no significant differences among groups in rates of ovulation (65-77%) or pregnancy (Exp. 2: 26-33%; Exp. 3: 39-43%). In Exp. 3, diameter of the dominant ovarian follicle on Day 9 was larger in heifers given 0.558 g vs 1.0 g P4 (10.3 ± 0.2 vs 9.3 ± 0.2 mm; P < 0.01). In conclusion, lesser amounts of P4 in the intravaginal device or PGF on Day 0 decreased plasma P4 from Days 1 to 8 and increased diameter of the dominant follicle on Day 9. However, neither of these nor 300 IU of eCG on Day 8 significantly increased rates of ovulation or pregnancy.

Effect of early luteolysis in progesterone-based timed AI protocols in Bos indicus, Bos indicus x Bos taurus, and Bos taurus heifers.

The objective of this study was to evaluate the effects of treatment with an intravaginal progesterone-releasing device (CIDR) and estradiol benzoate (EB) on follicular dynamics in Bos indicus (n=23), Bos taurus (n=25), and cross-bred (n=23) heifers. To assess the influence of reduced serum progesterone concentrations during 8 days of treatment with a progesterone-releasing device on follicular dynamics, half of the heifers received PGF at CIDR insertion (Day 0; 3 x 2 factorial design). Mean (+/-S.E.M.) serum progesterone concentrations during CIDR treatment varied (P<0.05) among genetic groups: B. indicus (5.4+/-0.1 ng/mL), B. taurus (3.3+/-0.0 ng/mL), and cross-bred (4.3+/-0.1 ng/mL). Maximum diameter of the dominant follicle (DF) was smaller (P<0.01) in B. indicus heifers (9.5+/-0.5 mm) than in cross-bred (12.3+/-0.4 mm) or B. taurus heifers (11.6+/-0.5 mm). B. indicus experienced lower (P<0.01) ovulation rate (39.1%) than did B. taurus (72.7%) and cross-bred (84.0%). Heifers treated with PGF on Day 0 had lower (P<0.05) serum progesterone concentrations during progesterone treatment. The PGF treatment on Day 0 increased (P<0.01) the diameter of the DF (11.9+/-0.4 mm vs. 10.5+/-0.4 mm). Moreover, greater (P=0.02) ovulation rates (78.8 vs. 54.0%) occurred in heifers treated with PGF on Day 0. In summary, B. indicus heifers had greater serum progesterone concentrations, smaller DF diameter, and a lower ovulation rate compared to B. taurus heifers. Prostaglandin treatment on the day of CIDR insertion reduced serum progesterone during treatment, and resulted in increased maximum DF diameter and ovulation rate.

Influence of prostaglandins on glucose transport in isolated rat uterus.

Glucose transport by uterine strips from ovariectomized estrogenized rats was explored. Sugar transport was significantly different from saccharose values (non-specific diffusion) only after 60 min of incubation. The addition of cytochalasin B demonstrated that we are measuring a specific mechanism for glucose transport. Insulin-enhanced sugar transport only at 0.5 or 0.25 U/ml prostaglandin E1 (PGE1), PGE2 and PGF2 alpha (10(-7) M) significantly improved glucose transport, but indomethacin (10(-6) M) failed in modifying this parameter in either control nor insulin-treated tissues. We did not observe an additive or synergistic action between PGE2 (10(-7) M) and insulin (used at maximal or submaximal concentration).

Effects of prostaglandin F2 alpha on vasoconstrictor responses in the mesenteric vascular bed.

Prostaglandin F2 alpha (PGF2 alpha) in a concentration that did not induce vascular contraction (10(-8) M) potentiated the dose-response curves to norepinephrine and 5-hydroxytryptamine and the contractile response induced by potassium (60 or 100 mM) in isolated mesenteric vascular bed of the rat. After prostaglandin inhibitor treatment with indomethacin (10(-6) M), the dose-response curve to norepinephrine was reduced, and the dose (10(-10) M) of PGF2 alpha, which was ineffective in control tissues, facilitated the norepinephrine contractile response. In contrast, indomethacin did not change either the contractile response induced by potassium or the PGF2 alpha potentiation of this response. Calcium antagonists diltiazem or flunarizine reduced the potassium-induced contractile response. After diltiazem treatment, 10(-10) M of PGF2 alpha was also effective in facilitating this response. The PGF2 alpha postjunctional effect was conserved after phosphoinositide hydrolysis inhibition. These results suggest that PGF2 alpha potentiation of the contractile response may be independent of PGF2 alpha contraction. Low doses of endogenous prostaglandins could be able to facilitate the norepinephrine contractile response in this tissue. This process may be independent of calcium influx and phosphoinositide hydrolysis.

El efecto prostaglandínico en la cámara anterior: su tratamiento / Prostaglandin effect in the anterior chamber: its treatment

Desde los trabajos de Ambache a partir de 1955, que demostraron que la sustancia a la que denominó Irin, era un compuesto de prostaglandinas E y F, se conoce que ellas son las responsables, a través de su presencia en la cámara anterior, de la hiperemia conjuntival, miosis, aumento del contenido proteico en el humor acuoso, disrupción de la barrera hemato-ocular y aumento de la presión intraocular. Efectuamos una revisión bibliográfica; propiciamos el uso de antinflamatorios no esteroideos, como inhibidores de la "PG" y presentamos una fórmula de aspirina soluble de uso tópico

El efecto prostaglandínico en la cámara anterior: su tratamiento / Prostaglandin effect in the anterior chamber: its treatment

Desde los trabajos de Ambache a partir de 1955, que demostraron que la sustancia a la que denominó Irin, era un compuesto de prostaglandinas E y F, se conoce que ellas son las responsables, a través de su presencia en la cámara anterior, de la hiperemia conjuntival, miosis, aumento del contenido proteico en el humor acuoso, disrupción de la barrera hemato-ocular y aumento de la presión intraocular. Efectuamos una revisión bibliográfica; propiciamos el uso de antinflamatorios no esteroideos, como inhibidores de la "PG" y presentamos una fórmula de aspirina soluble de uso tópico (AU)

Feto morto: II. Diagnóstico; resoluçäo do parto / Fetal death: II. Diagnosis; resolution of labor

Foram estudadas, retrospectivamente, 437 gestantes com diagnóstico de morte fetal, cujos partos foram realizados nos Hospital da Clínicas de Ribeiräo Preto, no período de 1.1.1978 a 31.12.1982. Foram analisados aspectos ligados ao diagnóstico da morte fetal e à resoluçäo do parto. Constatou-se o diagnóstico clínico predominou (52,41%) e o exame complementar mais utilizado foi a ecografia, suplantando o exame radiológico e a amniocentese. Houve sete casos com história clínica de morte fetal com mais de quatro semanas, sendo resolvidos sem nenhum problema materno, do ponto de vista hemorrágico. A induçäo ou a estimulaçäo do trabalho de parto foram utilizadas em 55,13% das vezes. O parto desencadeou-se espontaneamente nos 44,87% dos casos restantes. O parto foi normal em 79,85% das vezes e cirúrgico nas outras, a maioria por indicaçäo materna. A embriotomia foi realizada em 6,41% das oportunidades

Cell cycle regulation in mammalian cells: hormones and commitment to DNA synthesis.

The growth regulation of cultured mouse fibroblasts and functional adrenal cells was studied. Variants of mutants from these cell lines were obtained. The effects of classical hormones (insulin, hydrocortisone and adrenocorticotropin) and of growth factors (EGF and PF) were analysed. These hormones stimulate or inhibit the entry of cells into S phase. However G1 cells become irreversibly committed to DNA synthesis 5 hours before entering S phase.

Effects of prostaglandins upon hair growth in mice.

The effect of prostaglandins upon the diffuse hair wave induced by gonadectomy was studied in male C3H mice. The drugs used were Prostaglandin E1 and Prostaglandin F2alpha, tromethamine salt, which were administered twice a day intraperitoneally during 22 days, in daily doses from 1 to 6 micrograms. The animals had their back clipped and were castrated at the beginning of each experiment. At the end of the 22 day experimental period while all the castrated control mice were completely covered by hair, in the castrated prostaglandin treated mice a marked inhibition of the hair growth was noticed.