Ge-gen decoction alleviates primary dysmenorrhoea symptoms in a rat model.

BACKGROUND: Existing treatments for primary dysmenorrhoea (PD), such as NSAIDs, impart side effects. Ge-Gen decoction (GGD), a traditional Chinese medicine, has shown promise in treating PD, but its exact mechanisms remain unclear. Here, we aimed to investigate the efficiency of GGD in alleviating PD using a rat model to understand its precise mechanism of action. METHODS: We established a rat model of dysmenorrhoea induced by oestradiol and oxytocin. The PD rats were administered GGD or Ibuprofen (positive control) intragastrically once daily for seven consecutive days. Serum levels of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), ß-endorphin (ß-EP), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined using an enzyme-linked immunosorbent assay (ELISA). The expression levels of oestrogen receptor alpha (ERα) and cyclooxygenase-2 (COX-2) in uterine tissue were measured using immunohistochemical assays, and those of phosphorylated and total extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were assessed using western blot analysis. RESULTS: Treatment with GGD significantly reduced writhing behaviour, histopathological scores, and levels of COX-2, PGE2, and PGF2α in the serum of PD rats. Additionally, GGD increased ß-EP content and inhibited ERK1/2 activation and ERα expression in uterine tissues. CONCLUSIONS: The results of this study suggest that GGD alleviates PD in rats by suppressing the COX-2-mediated release of PGE2 and PGF2α, modulating the ERα/ERK1/2/COX-2 pathway, and increasing ß-EP content. These results provide insights into the potential mechanisms of GGD in treating PD and support its further investigation as an alternative therapy for this condition.

Ge-Gen decoction is commonly used to alleviate primary dysmenorrhoea. However, its anti-dysmenorrhoea mechanism remains elusive. In this study, using a rat model of primary dysmenorrhoea, we demonstrate that Ge-Gen decoction reduced the levels of cyclooxygenase-2, prostaglandin E2, and prostaglandin F2 alpha in serum and phosphorylated extracellular signal-regulated protein kinases 1 and 2 in the uterus. These results suggest that Ge-Gen decoction alleviates primary dysmenorrhoea via inactivation of the oestrogen receptor alpha/extracellular signal-regulated protein kinases 1 and 2/cyclooxygenase-2 pathway. This study enhances our understanding of the pathogenesis of primary dysmenorrhoea and may potentially inform the development of novel treatment approaches.

Disruption of multiple copies of the Prostaglandin F2alpha synthase gene affects oxidative stress response and infectivity in Trypanosoma cruzi.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a serious chronic parasitic disease, currently treated with Nifurtimox (NFX) and Benznidazole (BZ). In addition to high toxicity, these drugs have low healing efficacy, especially in the chronic phase of the disease. The existence of drug-resistant T. cruzi strains and the occurrence of cross-resistance between BZ and NFX have also been described. In this context, it is urgent to study the metabolism of these drugs in T. cruzi, to better understand the mechanisms of resistance. Prostaglandin F2α synthase (PGFS) is an enzyme that has been correlated with parasite resistance to BZ, but the mechanism by which resistance occurs is still unclear. Our results show that the genome of the CL Brener clone of T. cruzi, contains five PGFS sequences and three potential pseudogenes. Using CRISPR/Cas9 we generated knockout cell lines in which all PGFS sequences were disrupted, as shown by PCR and western blotting analyses. The PGFS deletion did not alter the growth of the parasites or their susceptibility to BZ and NFX when compared to wild-type (WT) parasites. Interestingly, NTR-1 transcripts were shown to be upregulated in ΔPGFS mutants. Furthermore, the ΔPGFS parasites were 1.6 to 1.7-fold less tolerant to oxidative stress generated by menadione, presented lower levels of lipid bodies than the control parasites during the stationary phase, and were less infective than control parasites.

Prevalence of subclinical endometritis in dairy cows that recovered after treatment of clinical endometritis with cephapirin and PGF2α.

The aims of our study were to evaluate (1) the prevalence of subclinical endometritis (SE) in clinically cured cows after treatment of clinical endometritis (CE) with uterine cephapirin infusion or with systemic application of PGF2α and after self-healing, (2) the prevalence of SE in clinically cured cows in relation to the type of vaginal discharge. The study was conducted on 222 Polish Holstein Friesian cows with CE diagnosed by vaginoscopy and ultrasound. The animals were randomly allocated to one of three groups: Group 1 (n = 72): intrauterine cephapirin infusion; Group 2 (n = 73): single intramuscular injection of dinoprost; and Group 3 (n = 77): left untreated as a control. All cows were reexamined two weeks later (Exam 1). If there was still CE at this examination, these cows were treated using the same method as previously and were examined 2 weeks later (Exam 2). Cows still having CE at the second examination were examined two weeks later (Exam 3). Cows without signs of CE at Exams 1, 2 and 3 were considered cured, and endometrial samples from the uteri were collected by cytobrush to diagnose SE using cytological evaluation of PMN percentage. The threshold for SE was set at ≥ 5% PMNs. Two cows each from Groups 1 and 3 and three cows from Group 2 were not clinically recovered at Exam 3 and were excluded from the analysis. In total, SE was diagnosed in an average of 40.9% of clinically cured cows. The prevalence of SE in Group 1, 2 and 3 was 35.0%, 47.1% and 40.0%, respectively (p > 0.05). There were significantly higher (p < 0.05) SE cases after treatment of CE associated with purulent vaginal discharge than with mucopurulent discharge. In relation to the method of treatment, the prevalence of SE was significantly higher (p < 0.05) in cows treated with cephapirin with purulent vaginal discharge than with mucopurulent vaginal discharge. In conclusion, the study showed a high prevalence of SE in cows clinically cured after treatment of clinical endometritis with cephapirin or PGF2α and after self-healing. The prevalence of SE was significantly higher in cows with purulent vaginal discharge than with mucopurulent vaginal discharge. Therefore, in cows clinically recovered from clinical endometritis, the prevalence of SE should always be considered a negative consequence, and the resulting management of this uterine disease should be implemented at the herd level.

NK1 receptor antagonistic effect of 17-trifluoromethyl phenyl trinor prostaglandin F2α on the growth of human breast cancer cell line.

BACKGROUND: A growing number of genetic and cancer biology investigations have found that the tachykinin NK1 Receptor plays an important role in cancer cell proliferation and survival. In this study. The present study was designed to evaluate the inhibition of cell growth by 17-trifluoromethyl phenyl trinor prostaglandin F2α with NK1 receptor in breast cancer cell lines. MATERIALS AND METHODS: MDB-MB-468 and MCF-7 breast cancer cell lines were used in the experiment were blocked with PGF2a. Cell proliferation and apoptosis were analyzed to evaluate the cytotoxic effect. Cell cycle distribution, Caspase-3 enzyme activity, Bad and Bax protein expression through flow cytometry and molecular docking were carried out to analyze the NK1 receptor activity. RESULTS: We found that PGF2a has a high binding affinity towards NK1 Receptor from molecular docking studies. It exerted cytotoxic and antiproliferative effects against MDB-MB-468 and MCF-7 breast cancer cell lines. Our data found that treatment of cells with 17-TPGF2 resulted in cell death and showed that increased expression of Caspase-3, Bad, and Bax protein and further induces G2 cell cycle arrest. CONCLUSION: Overall this study investigates the NK1 receptor antagonistic effect of PGF2 against breast cancer cell lines. However, further studies are needed to better characterize the application of NK1 receptor inhibition in clinical cancer treatment and cytotoxicity effect.

Evaluation of the effect of combined intralesional injection of prostaglandin F2α with narrow band UVB phototherapy in treatment of resistant cases of vitiligo.

BACKGROUND: Vitiligo is a chronic cutaneous disease characterized with hypopigmented patches that leave psychological impact on the patients. There is increasing need for new treatment modalities to shorten the duration of treatment of vitiligo with the least side effects. OBJECTIVE: To explore the effect of intralesional injection of prostaglandin F2α on the outcome of narrow band ultraviolet rays B (NBUVB) for patients with stable vitiligo. PATIENTS AND METHODS: The study included 27 stable vitiligo patients with overall symmetrical lesions. For each patient, one patch was treated with NBUVB alone (control side), while another symmetrical patch was treated with combined intralesional injection of prostaglandin F2α with NBUVB therapy, weekly for 3 months. RESULTS: There was statistically significant improvement in the repigmentation in the combination group compared with NBUVB group. Side effects were minimal. CONCLUSION: Intralesional injection of prostaglandin F2α in combination with NBUVB therapy could be considered as safe and tolerable technique for treatment of vitiligo, it shortens the duration of NBUVB therapy. Longer follow up is needed.

Serum biochemical profile in buffalo endometritis and impact of treatment with PGF2α and intrauterine gentamicin infusion on postpartum reproductive performance.

Improving reproductive performance of repeat breeder buffalo cows due to clinical endometritis is crucial in overcoming infertility problems in buffalo cows. The aim of the present study was to use PGF2α and/or gentamicin 10% for treatment of endometritis and to determine biochemical parameters in serum that could be used to diagnose endometritis in buffalo cows. A total of 64 anestrous buffalo cows were assigned into one of five treatment groups: group one (n = 9) buffalo cows were physiological normal cows and served as a control group; group 2 buffalo cows had endometritis, but were not treated (n = 10); group 3 buffalo cows had endometritis and were treated with intrauterine delivery of 100 ml of a 10% gentamicin sulfate solution in three times within 1 week (n = 15); group 4 buffalo cows received two I.M. doses of PGF2α (2 ml Estrumate IM) at the time of corpus luteum dominance (n = 15) (treatment 4 does not make sense as you stated that the cows were in anestrus) on the ovary; group 5 buffalo cows received two IM doses of PGF2α at an 11 day interval and the 10% gentamicin solution as described for group 3. Serum samples were collected from control, pre-treated, and post-treated buffalo cows with endometritis to evaluate the diagnostic biochemical parameters. The days to first estrus (DFE), number of services per conception (S/C), days open (DO), and pregnancy rate (Preg) were the measures for determining reproductive performance for the buffalo cows. The buffalo cows treated by gentamicin and PGF2 exhibited their first estrus earlier than cows in the other four groups of cows. The number of days open for control cows was greater (P < 0.05) than for the other groups and the control cows, as were the number of services per conception (P < 0.05) and pregnancy rate (30%: P < 0.05). The receiver operating characteristic (ROC) curve was used to identify biochemical parameters in serum to predict endometritis. Creatine kinase (CK), aspartate aminotransferase (AST), and concentrations of total bilirubin and immunoglobulins in serum were greater (P < 0.05), while serum albumin values were lower (P < 0.05) in serum of buffalo cows with endometritis. From the ROC analyses, CK was the most predictable biomarker for endometritis with an area under the curve of 0.889, sensitivity of 80%, and specificity of 100% (P < 0.001). In conclusion, the use of gentamicin and PGF2 for treatment of endometritis improves the reproductive performance of buffalo cows, and concentrations of CK serve as an aid for diagnosing endometritis.Graphical abstract.

Effect of Topical Prostaglandin F2α Analogs on Selected Oxidative Stress Parameters in the Tear Film.

Background and Objectives: Topically administered antiglaucoma medications, especially those containing benzalkonium chloride (BAC), may cause local adverse effects and compromise ocular surface. The aim of the study was to assess the effect of topical prostaglandin F2α analogs (PGAs): preservative-free latanoprost, BAC-preserved latanoprost, preservative-free tafluprost, and BAC-preserved bimatoprost, on selected oxidative stress parameters in the tear film. Materials and Methods: The patients were divided into five groups: group C (n = 25) control group-subjects who did not use topical antiglaucoma medications, group L (n = 22)-patients using topical preservative-free latanoprost, group L+BAC (n = 25)-patients using topical BAC-preserved latanoprost, group T (n = 19)-patients using topical preservative-free tafluprost, and group B+BAC (n = 17)-patients using topical BAC-preserved bimatoprost. The oxidative stress markers in the tear film samples were evaluated: total protein (TP) concentration, advanced oxidation protein products (AOPP) content, total sulfhydryl (-SH) groups content, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as Total Oxidant Status (TOS), Total Antioxidant Response (TAR), and Oxidative Stress Index (OSI). Results: The TP concentrations in the groups L, L+BAC, and B+BAC were statistically significantly higher in comparison with group C. The SOD and CAT activities in the groups L+BAC and B+BAC were statistically significantly higher when compared to group C. As compared to group C, AOPP and TOS were statistically significantly higher in all the study groups. OSI was found to be statistically significantly higher in the groups L+BAC, T, and B+BAC in comparison with group C. Conclusion: Use of topical PGAs by the patients with ocular hypertension or primary open-angle glaucoma is associated with increased oxidative stress in the tear film which is additionally exacerbated by the presence of BAC in the formulation.

The impact of ecbolic therapy in the early postpartum period on uterine involution and reproductive health in dairy cows.

Postpartum uterine disease due to poor uterine involution continues to be a significant factor that contributes to poor reproductive efficiency in dairy cattle. Therapy that increases the frequency, duration and strength of uterine contractions in the postpartum period might enhance uterine involution, resulting in improved reproductive performance. The objective of this clinical trial was to study the effect of two uterine ecbolic therapies, oxytocin and prostaglandinF2α on uterine involution, postpartum endometritis, and reproductive performance. A randomized double-blinded clinical trial was conducted in 118 dairy cows from two research herds that had normal parturition and expulsion of the fetal membranes. Within 24 hr after calving, cows were randomly assigned to receive intramuscular injections twice a day of 50 IU of oxytocin, or 25 mg of dinoprost (PGF2α) or saline (control) for 7 days. Cows were monitored from day 3 to day 63 ± 3 days postpartum by transrectal palpation of the uterus, vaginoscopy, Metricheck® examination and by endometrial cytology. Blood samples were collected for measurement of progesterone in weeks 3 (21 ± 3 days), 5 (35 ± 3 days), 7 (49 ± 3 days), and 9 (63 ± 3 days) postpartum. Herd breeding records were obtained to determine reproductive performance in all cows. Neither oxytocin nor prostaglandin F2α therapy during the first week postpartum had any significant effect on the rate of uterine involution, prevalence of endometritis or reproductive performance, compared to untreated controls. Ecbolic drugs, as used here, are not recommended for use in clinical practice to improve involution or reproductive tract health in normal cows.

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.

Endometrial prostaglandin F2α in vitro production and its modulation regarding dominant follicle position in cattle / Produção in vitro de PGF F2α endometrial e sua modulação referente ao folículo dominante em bovinos

Prostaglandin F2α (PGF2α) determines luteolysis in cattle, and the ability to manipulate its endogenous synthesis is indispensible for large-scale animal breeding. Estradiol (E2) and progesterone (P4) modulate several molecular pathways in endometrial cells, including the synthesis of PGF2α; however, its specific mechanisms are still not totally known. This study investigated the production in vitro and possible modulation of endometrial PGF2α due to a local effect of endogenous E2 in the ipsilateral uterine horn (UH) containing the dominant follicle (DF) or from P4 in ipsilateral horn containing the corpus luteum (CL). The PGF2α stimulators oxytocin (OT) and phorbol 12,13-dibutyrate (PDBu) were incubated with endometrial explants, and PGF2α content was measured. For that, cycling cows were synchronized, the development of DF and CL was examined by ultrasonography and on the seventh day of the estrous cycle, endometrial explants were collected and cultured in medium supplemented with 10-6 M PDBu or 10-6 M OT or non-supplemented. Media samples were collected immediately after treatment and 60 min later. Radioimmunoassay showed that the PGF2α content of the UH ipsilateral to the DF was 49% less than that of the contralateral UH (8.22 ± 0.95 vs. 12.24 ± 0.95 pg/mL/mg tissue, respectively; P < 0.01). However, the PGF2α levels did not differ between the UHs as a function of the CL position (9.46 ± 0.95 vs. 11 ± 0.95 pg/mL/mg; P > 0.05). The cellular stimulators promoted an increase in PGF2α synthesis (P < 0.02), and the effects differed among the animals (P < 0.04). The PGF2a production was higher in the explants treated with PDBu rather than OT (13.68 ± 1.16 vs. 10.01 ± 1.16 pg/mL/mg tissue, respectively; P < 0.05). In conclusion, PGF2α synthesis is modulated by the presence of the DF (local E2) but not the CL (local P4), and both PDBu and OT stimulated PGF2a synthesis.(AU)

A prostaglandina F2α (PGF2α) determina a luteólise em bovinos. A capacidade de manipular sua síntese endógena é indispensável para a produção animal em grande escala. O estradiol (E2) e a progesterona (P4) modulam diversas vias moleculares das células endometriais, incluindo a síntese de PGF2α; no entanto, pouco se sabe sobre seus mecanismos específicos. Este trabalho investigou a produção in vitro e a possível modulação da PGF2α endometrial devido a um efeito local do E2 endógeno no corno uterino ipsilateral ao folículo dominante (FD) ou da P4 no corno ipsilateral ao corpo lúteo (CL). Os estimuladores de PGF2α oxitocina (OT) e 12,23-dibutirato de forbol (PDBu) foram incubados com explantes endometriais, e o conteúdo de PGF2α foi mensurado. Para tal, vacas cíclicas foram sincronizadas, o desenvolvimento de FD e CL foi examinado por ultrassonografia, e no 17º dia do ciclo estral os explantes endometriais foram coletados e cultivados em meio ou suplementados com PDBu 10-6M ou 10-6M OT. As amostras de meio foram coletadas imediatamente após o tratamento e sessenta minutos depois. O radioimunoensaio mostrou que o conteúdo de PGF2α do corno ipsilateral ao FD foi 49% menor que o do corno contralateral (8,22 ± 0,95 vs. 12,24 ± 0,95 pg/mL/mg de tecido, respectivamente, P < 0,01). No entanto, os níveis de PGF2α não diferiram entre os cornos em função da posição do CL (9,46 ± 0,95 versus 11 ± 0,95 pg/mL/mg; P > 0,05). Os estimuladores celulares promoveram um aumento na síntese de PGF2α (P < 0,02), e os efeitos diferiram entre os animais (P < 0,04). A produção de PGF2α foi maior nos explantes tratados com PDBu em comparação à OT (13,68 ± 1,16 versus 10,01 ± 1,16 pg/mL/mg de tecido, respectivamente, P < 0,05). A conclusão obtida foi que a síntese de PGF2α é: modulada pela presença do FD (E2 local), mas não do CL (P4 local); e estimulada por PDBu e OT.(AU)

Reproductive performance in dairy cows with cystic ovarian disease after single treatment with buserelin acetate or dinoprost.

The treatment of cystic ovarian disease (COD) in dairy cows is still controversial, and some researchers recommend using gonadotropin-releasing hormone (GnRH) regardless of the type of cysts. The aim of this study was to comparatively evaluate the reproductive performance of cows diagnosed with follicular or luteal cystic structures, after treatment with either buserelin acetate (GnRH agonist) or dinoprost (prostaglandin F2-alpha or PGF2α). The diagnosis was established by ultrasonographic examinations performed twice a month starting 40-45 days after calving, until the cows were diagnosed pregnant after artificial insemination. Both types of cysts were treated either with 21 µg buserelin acetate or 25 mg dinoprost, resulting in four subject groups. After treatment, the estrus rate in cows with follicular cysts treated with dinoprost (55.1%) was significantly lower (P<0.05) than in cows treated with buserelin acetate (77.5%) or in cows diagnosed with luteal cysts (77.2% for dinoprost and 72.4% for buserelin acetate). The conception rate was higher (P<0.05) in cows with follicular cysts treated with buserelin acetate (67.7%) than in those treated with dinoprost (60%) or in those with luteal cysts (56.9% for dinoprost and 47.5% for buserelin acetate). These results show that it is preferable to differentiate between the two types of ovarian cysts before treatment. Luteal cysts can be treated with either PGF2α or GnRH analogues, with better results when PGF2α is used. Contrastingly, follicular cysts are better treated with GnRH analogues. When differentiation is not possible, GnRH analogues are recommended over PGF2α.

Effect of diagnosis and treatment of clinical endometritis based on vaginal discharge score grading system in postpartum Holstein cows.

In this study, the prevalence, effectiveness of diagnosis, and treatment based on vaginal discharge score (VDS) of clinical endometritis in cattle were evaluated. To detect clinical endometritis and classify its severity, vaginoscopy was performed during 21 to 60 days postpartum in 164 Holstein cows consisting of 229 lactations. Groups were defined using the 4-point VDS scale. Study groups included the following: non-endometritis (VDS=0; no/clear mucus; NEM group; n=168); mild endometritis, no treatment (VDS=1; mucus containing flecks of white/off-white pus; NTR group; n=30); and severe endometritis, treated with PGF2α (VDS≥2; discharge containing <50% pus; and VDS=3; discharge containing >50% pus, and fluid or uterine horn asymmetry; TEM group; n=31). Cows treated with PGF2α that did not recover (VDS≥1, n=5) received intrauterine procaine penicillin and streptomycin. Prevalence of clinical endometritis (VDS≥1) was 26.6%. The NTR group required significantly more artificial inseminations per pregnancy than NEM and TEM groups (2.8 ± 1.8 vs 2.0 ± 1.3, 1.9 ± 0.8, P<0.05). In survival analysis, the proportion of non-pregnant cows was higher in the NTR group compared to the NEM (P=0.012) and TEM (P=0.076) groups. In the TEM group, calving to first artificial insemination interval tended to be higher in cows treated 41 to 60 days postpartum than cows treated 29 to 40 days postpartum (97.2 ± 27.1 vs 74.4 ± 19.7, P=0.084). Our study suggests that cows with VDS=1 may require treatment to recover fertility. Diagnosis and treatment of clinical endometritis based on a VDS grading system may improve dairy herd reproductive performance.

Physicochemical and biological characterization of sustained isopropyl unoprostone-release device made of poly(ethyleneglycol) dimethacrylates.

Transscleral drug delivery is becoming increasingly popular to manage posterior eye diseases. To evaluate the clinical application of a transscleral, sustained, unoprostone (UNO)-release device (URD) constructed of photopolymerized tri(ethyleneglycol) dimethacrylate and poly(ethyleneglycol) dimethacrylate, we evaluated physicochemical and biological properties of this device. The URD consists of a drug-impermeable reservoir and a semi-permeable cover. The in vitro release rate of UNO from the URD increased with increasing temperatures from 20 to 45 °C. Scanning electron microscopy and atomic-force microscopy showed that the border between the reservoir and drug formulation was sharply defined but that between the cover and drug was poorly determined, indicating that UNO could permeate only through the cover. For stability tests, the URDs were sterilized with ethylene oxide gas and stored at 40 °C/75% for 3 and 6 months and at 25 °C/60% for 3, 6, 9, 12, 18, and 24 months; UNO content and release rate at 37 °C were then evaluated. There was no significant decrease in either UNO content or release rate after the storage conditions. Cytotoxicity was evaluated by examining the colony formation of Chinese hamster fibroblast V79 cells in a media extract of the URD without UNO. This extract did not affect colony formation of V79 cells, indicating the cytocompatibility of the URD. In conclusion, the URD was physically stable for 24 months and is potentially useful for clinical application.

Purulent vaginal discharge in grazing dairy cows: Risk factors, reproductive performance, and prostaglandin F2α treatment.

The objectives of this study were to assess the association of a 4-point scale of vaginal discharge score (VDS) with time to pregnancy to define criteria for a practical case of purulent vaginal discharge (PVD) in dairy cows, to test the risk factors for PVD, and, finally, the effect of a dose of PGF2α on cure and reproductive performance. In experiment 1, grazing Holstein cows (n = 2,414) had their vaginal discharge scored at ∼32 d in milk (DIM) on a 4-point scale, the effect of VDS on the hazard of pregnancy by 300 DIM was then assessed to derive a case definition of PVD. Risk factors for PVD and self-cure were also assessed. In experiment 2, grazing Holstein cows (n = 6,326) from 5 herds were checked for PVD at ∼30 DIM. Cows with PVD were assigned to receive one dose of 500 µg of PGF2α analog (Cloprostenol; Ciclase, Syntex SA, Buenos Aires, Argentina) per cow (odd ear tag number) or to remain untreated (even tag number). Cure was declared if cows presented clear normal vaginal discharge (VDS-0) at visit 2 (∼62 DIM). Data were analyzed with Cox's regression and mixed logistic models. In experiment 1, cows with VDS ≥1 had lower hazard of pregnancy and longer calving to pregnancy interval than cows with VDS-0. This finding was not affected by the time at which the diagnosis was performed. Therefore, a cow ≥21 DIM and having VDS ≥1 was used to define a case of PVD. The odds of PVD were greater in primiparous cows compared with multiparous, in cows with abnormal calving compared with those with normal calving, and in those losing BCS peripartum. In experiment 2, PGF2α treatment tended to slightly increase the hazard of pregnancy (adjusted hazard ratio = 1.13). Conversely, PGF2α had no effect on the odds of cure of PVD [adjusted odds ratio (AOR) = 1.19], pregnancy at first service (AOR = 1.03), or pregnancy by 100 DIM (AOR = 0.89) or 200 DIM (AOR = 1.27). In conclusion, cows with VDS ≥1 can be considered to have PVD because of their lower hazard of pregnancy and longer calving to pregnancy interval (up to 48 d). Important risk factors are parity, calving, and body condition score loss peripartum. Optimal time of diagnosis is ≥28 to 35 DIM because cows experience a high self-cure rate. Self-cure is also affected by parity, prepartum BCS, and VDS. Finally, as treatment with one dose of PGF2α had a small effect on the hazard of pregnancy and no effect on clinical cure, its therapeutic use in grazing dairy cows with PVD is not recommended.

Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration.

BACKGROUND: To evaluate the efficacy and safety of topical isopropyl unoprostone (IU) in treating macular atrophy in age-related macular degeneration (AMD) patients. METHODS: Fifty-two AMD patients with macular atrophy were included and randomly assigned (1:1) to the treatment (topical 0.15% IU) or placebo group. Subjects used study eye drops 3 times a day for 54 weeks. The macular atrophy was documented on fundus autofluorescence photographs and measured using RegionFinder. The enlargement rate of macular atrophy and the changes in visual acuity were examined statistically between baseline and 54 weeks. RESULTS: Forty-eight subjects were included in the analyses because 4 subjects withdrew from the study. The differences between the IU and placebo groups in mean and median area of macular atrophy were not statistically significant at baseline. The baseline median lesion size of macular atrophy was 2.33 mm in the IU group and 1.63 mm in the placebo group (P = 0.51). The intergroup difference in the enlargement ratio of macular atrophy (21 ±â€Š15% in the IU group and 111 ±â€Š96% in the placebo group) was statistically significant (P < 0.001). Additionally, visual acuity tended to improve over baseline in the IU group. No serious adverse events were observed. CONCLUSIONS: Topical IU therapy is safe and effective for treating macular atrophy in AMD patients.

A weekly postpartum PGF2α protocol enhances uterine health in dairy cows.

Postpartum uterine health in dairy cows is crucial for the maintenance of good reproductive performance. In order to improve uterine health and reduce puerperal intrauterine infection, 608 Holstein cows received a weekly PGF2α protocol (3 i.m. injections of PGF2α at 7, 14 and 21 d postpartum). For comparison, 593 cows in the control group received injections of sterile saline at the same time. Uterine score at 14 d postpartum, the prevalence of endometritis at 21-27 d postpartum, and subsequent reproduction performance was evaluated. Cows in the treated group exhibited higher tonicity (P<0.05) of the uterus, with less prevalence of endometritis (10.4%, 63/608 vs. 34.6%, 205/593; P<0.001), and required shorter time to the first AI postpartum (67.5±3.4 d vs. 84.4±3.7 d, P<0.05) and to pregnancy (114.5±5.4 d vs. 131.4±5.8 d, P<0.05). In conclusion, the present study demonstrated that uterine health in Holstein cows can be promoted while puerperal infection can be suppressed by this weekly postpartum PGF2α protocol.

Pregnancy rate in dairy cows treated with progesterone for six days during estrus synchronization with PGF2α.

The present study evaluated the effect of progesterone supplementation during a double PGF2α injection synchronization protocol on pregnancy per artificial insemination (P/AI) and on the incidence of twin births. Seven hundred and eighty three dairy cows were synchronized with two injections of PGF2α 14 days apart, starting on day 35 postpartum for their first postpartum insemination. Six days before the second PGF2α injection, cows were treated either with a progesterone-releasing intravaginal device (PRID-Delta) and an intramuscular injection of 500mg of progesterone (n=387) or served as control (n=396) and did not receive progesterone treatment. Cows were inseminated 12h after being detected in estrus. Pregnancy was diagnosed 40-45 days later by transrectal palpation. Progesterone administration improved (P<0.05) the percentage of cows detected in estrus in multiparous [(192/255) 75% vs (161/267) 60%], but not in primiparous cows [93/132 (70%) vs 90/129 (70%)]. Progesterone treatment increased P/AI in multiparous [53/192 (28%) vs 27/161 (17%)] but not in primiparous cows [25/93 (27%) vs 29/90 (32%)]. The incidence of twin births tended to be lower (P=0.09) in cows treated with progesterone [1/74 (1%)] than in the control group [4/53 (7%)]. It is concluded that progesterone administration during estrus synchronization with two PGF2α injections in dairy cows improves estral response and increases P/AI in multiparous, but not in primiparous cows, and tended to decrease the incidence of twin births.

The 9-day CIDR-PG protocol: Incorporation of PGF2α pretreatment into a long-term progestin-based estrus synchronization protocol for postpartum beef cows.

A pilot experiment was designed to test the hypothesis that administration of PGF2α before progestin treatment would allow for a reduced duration of progestin treatment in a long-term progestin-based estrus synchronization protocol. A modified presynchronization treatment was compared with a standard long-term controlled internal drug release (CIDR) treatment, and treatments were compared on the basis of ovarian follicular dynamics, estrous response rate, synchrony of estrus expression, and pregnancy rates resulting from timed artificial insemination (TAI) in postpartum beef cows. Estrous was synchronized for 85 cows, with cows assigned to one of two treatments based on age, days postpartum, and body condition score. Cows assigned to the 14-day CIDR-PG protocol received a CIDR insert (1.38 g progesterone) on Day 0, CIDR removal on Day 14, and administration of PGF2α (25 mg im) on Day 30. Cows assigned to the 9-day CIDR-PG protocol received PGF2α concurrent with CIDR insertion on Day 5, PGF2α concurrent with CIDR removal on Day 14, and administration of PGF2α on Day 30. In both treatments, split-time AI was performed based on estrous response. At 72 hours after PGF2α (Day 33), cows having expressed estrus received TAI; cows that failed to express estrus by 72 hours received TAI 24 hours later (96 hours after PGF2α on Day 34), with GnRH (100 µg im) administered to nonestrous cows. Estrus-detection transmitters were used from CIDR removal until AI to determine onset time of estrus expression both after CIDR removal and after PGF2α. Ovarian ultrasonography was performed at CIDR removal on Day 14, PGF2α on Day 30, and AI on Days 33 or 34. At CIDR removal on Day 14, diameter of the largest follicle present on the ovary was similar between treatments. The proportion of cows expressing estrus after CIDR removal tended to be higher (P = 0.09) among cows assigned to the 9-day CIDR-PG treatment (93%; 40 of 43) than among cows assigned to the 14-day CIDR-PG treatment (81%; 34 of 42). After PGF2α, a significantly higher proportion (P = 0.02) of cows expressed estrus after synchronization with the 9-day CIDR-PG treatment (91%; 39 of 43) than the 14-day CIDR-PG treatment (69%; 29 of 42). Consequently, pregnancy rate to TAI tended to be increased (P = 0.09) among the 9-day CIDR-PG treatment (76.7%; 33 of 43) compared with the 14-day CIDR-PG treatment (59.5%; 25 of 42). In summary, a long-term CIDR-based estrous synchronization protocol for postpartum beef cows was enhanced through administration of PGF2α at CIDR insertion and CIDR removal.

Effects of different regimens of PGF2α treatment during postpartum on reproductive performance in dairy cows / Efeito de diferentes regimes de tratamento pós-parto com PGF2α sobre o desempenho reprodutivo de vacas leiteiras

The aim of this study was to evaluate the effects of early postpartum PGF2α treatment on reproductive performance in dairy cows synchronized with targeted breeding and natural mating after voluntary waiting period. In this experiment ,120 cows were assigned to three groups irrespective of presence or absence of luteal tissue. Cows in PG- 14 group were treated with PGF2α from day 14 postpartum, cows in PG-28 group were treated with PGF2α from day 28 postpartum and cows in PG-42 group were not treated with PGF2α until the end of voluntary waiting period (d 42). After day 42 postpartum, cows in three groups were treated with PGF2α within 14-day intervals until natural mating after voluntary waiting period. Recorded reproductive parameters included days to first heat, days to first mating, days open, service per conception, conception rate, percentage of repeat breeder animals and pregnancy loss. Early PGF2α treatment from day 14 postpartum significantly decreased days to first estrus (34.9 ± 0.74, P < 0.003), days to first mating (62.35 ± 1.53, P < 0.04), days open (117.23 ± 3.1, P < 0.001) and service per conception (1.9 ± 0.09, P < 0.02); and PG-14 group presented increased conception rate (52.5%, P < 0.05). The proportion of repeat breeder syndrome tended to be affected by treatment with PGF2α from day 14 postpartum. In conclusion, treatment of cows with PGF2α from day 14 postpartum improved reproductive performance.(AU)

O objetivo do presente trabalho foi avaliar os efeitos do tratamento pós-parto precoce com PGF2α sobre o desempenho reprodutivo de vacas leiteiras sincronizadas para reprodução controlada por monta natural após o período de espera voluntário. Neste experimento, 120 vacas foram distribuídas em três grupos independentes da presença ou ausência de corpo lúteo. Vacas no grupo PG-14 foram tratadas com PGF2α a partir do 14o dia pósparto, vacas do grupo PG-28 foram tratadas com PGF2α a partir do 28o dia pós-parto e as vacas do grupo PG-42 não foram tratadas com PGF2α até o final do período de espera voluntário (d42). Após o 42o dia pós-parto as vacas dos três grupos foram tratadas com PGF2α com intervalos de 14 dias até a monta natural após o período de espera voluntário. Os registros dos parâmetros reprodutivos incluíram: dias para o primeiro estro, dias para a primeira cobertura, dias em aberto, serviços por concepção, taxa de concepção, percentagem de animais repetidores de cios e as perdas de gestações. O tratamento precoce com PGF2α, a partir do 14o dia pós-parto reduziu significativamente os dias para o primeiro estro (34,9 ± 0,74, P < 0,003), dias para a primeira cobertura (62,35 ± 1,53, P < 0,04), dias em aberto (117,23 ± 3,1, P< 0,02); e o grupo PG-14 apresentou um acréscimo na taxa de concepção (52,5%, P < 0,05). A proporção da síndrome de vacas repetidoras de cios tendeu a ser afetada pelo tratamento com PGF2α a partir do 14o dia pós-parto. A conclusão obtida foi que o tratamento das vacas com PGF2α a partir do 14o dia pós-parto melhorou o desempenho reprodutivo dos animais.(AU)

Selective modulation of the prostaglandin F2α pathway markedly impacts on endometriosis progression in a xenograft mouse model.

STUDY HYPOTHESIS: Selective activation or blockade of the prostaglandin (PG) F2α receptor (FP receptor) affects ectopic endometrial tissue growth and endometriosis development. STUDY FINDING: FP receptor antagonists might represent a promising approach for the treatment of peritoneal endometriosis. WHAT IS KNOW ALREADY: Eutopic and ectopic endometrium from women with endometriosis exhibit higher expression of key enzymes involved in the PGF2α biosynthetic pathway. It has also been shown that the PGF2α-FP receptor interaction induces angiogenesis in human endometrial adenocarcinoma. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: For this study, a mouse model of endometriosis was developed by inoculating human endometrial biopsies into the peritoneal cavity of nude mouse (n = 15). Mice were treated with AL8810 (FP receptor antagonist), Fluprostenol (FP receptor agonist) or PBS. Endometriosis-like lesions were collected and analysed for set of markers for angiogenesis, tissue remodelling, apoptosis, cell proliferation and capillary formation using qPCR and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: We found that selective inhibition of the FP receptor with a specific antagonist, AL8810, led to a significant decline in the number (P < 0.01) and size of endometriosis-like lesions (P < 0.001), down-regulated the expression of key mediators of tissue remodelling (MMP9, P < 0.05) and angiogenesis (VEGF, P < 0.01) and up-regulated the pro-apoptotic factor (Bax, P < 0.01) as compared with controls. Immunohistochemical analyses further showed a marked decrease in cell proliferation and capillary formation in endometrial implants from AL8810-treated mice, as determined by proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) immunostaining, respectively. Moreover, Fluprostenol, a selective FP receptor agonist, showed the opposite effects. LIMITATIONS, REASONS FOR CAUTION: We carried out this study in nude mice, which have low levels of endogenous estrogens which may affect the lesion growth. Caution is required when interpreting these results to women. WIDER IMPLICATIONS OF THE FINDINGS: This study extends the role of PG signalling in endometriosis pathogenesis and points towards the possible relevance of selective FP receptor antagonism as a targeted treatment for endometriosis. LARGE SCALE DATA: Not Applicable. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by grant MOP-123259 to the late Dr Ali Akoum from the Canadian Institutes for Health Research. The authors have no conflict of interest.