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International Journal of Molecular... Apr 2023Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the...
Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves' ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.
Topics: Humans; Dinoprost; Adipogenesis; Extracellular Signal-Regulated MAP Kinases; Graves Ophthalmopathy; Fibroblasts; Cells, Cultured
PubMed: 37108173
DOI: 10.3390/ijms24087012 -
Journal of Dairy Science May 2023Increasing progesterone (P4) during early conceptus development may be crucial for establishment of pregnancy in dairy cattle. The objective of this study was to...
Increasing progesterone (P4) during early conceptus development may be crucial for establishment of pregnancy in dairy cattle. The objective of this study was to determine if human chorionic gonadotropin (hCG) at various times after ovulation will increase serum P4 during elongation and increase the chances for, and reduce variability to, initial increase in pregnancy-specific protein B (PSPB) following artificial insemination (AI). Time to PSPB increase was defined as the first day of increase in concentrations of PSPB between d 18 and 28 after ovulation in cows with ≥12.5% increases for 3 consecutive days compared with baseline. Lactating cows (n = 368) synchronized to Double-Ovsynch (first service) or Ovsynch (second or greater service) received one of 4 treatments: no hCG (control), or 3,000 IU of hCG on d 2 (D2), 2 and 5 (D2+5), or 5 (D5) after ovulation. All cows were examined via ultrasound on d 5 and 10 postovulation to determine percentage of cows with hCG-induced accessory CL (aCL) and to quantify and measure all luteal structures. Samples for serum P4 were collected on d 0, 5, 19, and 20 postovulation. The P4 was increased in D2, D2+5, and D5 groups compared with control. The D2+5 and D5 treatments increased aCL and P4 compared with D2 and control. The D2 treatment increased P4 on d 5 after ovulation compared with control. Serum PSPB samples were collected daily from all cows on d 18 through 28 after ovulation for determination of d of PSPB increase. Pregnancy diagnoses were performed via ultrasound examination on d 35, 63, and 100 after ovulation and AI. The D5 treatment reduced percentage of cows with, and increased the time to, PSPB increase. Primiparous cows with ipsilateral aCL had reduced pregnancy loss before d 100 postovulation compared with cows with contralateral aCL. Cows that had PSPB increase >21 d postovulation had 4× greater chances of pregnancy loss compared with cows that had PSPB increase on d 20 or 21. The highest quartile of P4 on d 5, but not on d 19 and 20, was associated with reduced time to PSPB increase. Time to PSPB increase appears to be an important measurement to understand reasons for pregnancy loss in lactating dairy cows. Increasing P4 utilizing hCG after ovulation did not enhance early pregnancy or reduce pregnancy losses in lactating dairy cows.
Topics: Pregnancy; Female; Humans; Cattle; Animals; Progesterone; Lactation; Estrus Synchronization; Chorionic Gonadotropin; Insemination, Artificial; Gonadotropin-Releasing Hormone; Dinoprost
PubMed: 37028965
DOI: 10.3168/jds.2022-22553 -
Journal of Ocular Pharmacology and... May 2023Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through... (Review)
Review
Prostaglandin analogue topical medications are one of the most effective therapeutic approaches for the chronic management of glaucoma and ocular hypertension, through the reduction of elevated intra ocular pressure (IOP). While many of the first generations of anti-glaucoma eye drops were preserved with benzalkonium chloride, their repeated use may induce chronic ocular surface toxicity that leads to ocular surface disease (OSD) signs and symptoms. As a result, soft-preservatives and preservative-free formulations have been developed with the goal to avoid the long-term iatrogenic toxicity of the preservative agents. In addition, it has been suggested that OSD and its associated inflammation may negatively impact the efficacy of the IOP-lowering medications, including treatment adherence and compliance. Hence, it may be particularly interesting that glaucoma medications can concomitantly protect and "heal" the ocular surface and its environment while lowering elevated IOP, for the greater benefit of glaucoma patients. The objective of the present review is to briefly present the preclinical data of the cationic oil-in-water emulsion of latanoprost (latanoprost-CE) to shed some light on its mechanisms of action. It overall supports the following hypothesis: the restoration of a healthy ocular surface environment and treatment of the OSD signs and symptoms will allow for an improved elevated IOP reduction and glaucoma management. This would be achieved with a once daily dosing regimen to preserve glaucoma patients' vision, ocular surface, and quality-of-life and wellness.
Topics: Humans; Latanoprost; Glaucoma, Open-Angle; Emulsions; Intraocular Pressure; Prostaglandins F, Synthetic; Antihypertensive Agents; Glaucoma; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical
PubMed: 37015075
DOI: 10.1089/jop.2022.0155 -
Veterinary Medicine and Science May 2023Ocular hypertension is one of the most underdiagnosed ocular abnormalities among guinea pigs around the world.
BACKGROUND
Ocular hypertension is one of the most underdiagnosed ocular abnormalities among guinea pigs around the world.
OBJECTIVES
The current study investigates the effect of 0.0015% preservative-free tafluprost ophthalmic solution (Zioptan) on the intraocular pressure of 16 healthy male guinea pigs (Cavia porcellus) under different light/darkness regimes.
METHODS
All guinea pigs received a single drop of tafluprost at 5:30 in the right eye, whereas the contralateral eyes served as control to receive a placebo. Then, the animals were randomly divided into two groups; group A was exposed to light, whereas group B was placed in darkness from 5:30 to 18:00. Rebound tonometry (TonoVet) was instrumented to measure IOP values at 5:30 (baseline), 6:00, 7:00, 8:00, 9:00 and then every 3 h until 18:00.
RESULTS
The maximum IOP reduction associated with tafluprost was observed at 6:00 by -1.4 ± 1.1 mmHg (p-value = 0.026) and -2.5 ± 1.2 mmHg (p-value = 0.011) in group A and B, respectively (repeated measure ANOVA test). There was a significant difference between the mean right and left eye IOP values in both groups at 5:30, 6:00, 7:00 and 8:00 (p-value <0.05), which was greater in amount in group B compared to group A due to the effect of darkness on IOP reduction.
CONCLUSIONS
It is suggested that the variations of IOP in different light/dark conditions be taken into consideration when applying ocular hypotensive agents on guinea pigs' eyes.
Topics: Guinea Pigs; Male; Animals; Intraocular Pressure; Darkness; Tonometry, Ocular; Prostaglandins F
PubMed: 36757117
DOI: 10.1002/vms3.1082 -
Medicine Dec 2022It is difficult to follow changes in the intraocular pressure (IOP) in glaucomatous eyes comprehensively because of the limited number of outpatient examinations. We...
RATIONALE
It is difficult to follow changes in the intraocular pressure (IOP) in glaucomatous eyes comprehensively because of the limited number of outpatient examinations. We report our findings in a case of normal tension glaucoma (NTG) in which frequent self-measurements of the IOP were used to evaluate the IOP-lowering effect of different medications.
PATIENT CONCERNS
A 50-year-old man with NTG had a nasal step visual field defect in his right eye and was being treated with 0.005% latanoprost (LAT) ophthalmic solution (XALATAN®).
DIAGNOSIS
The patient was diagnosed with NTG.
INTERVENTIONS
The patient had a mean IOP in the right eye of 10.9 ± 1.5 mm Hg (68 measurements in 1 month, Period A) during treatment with 0.005% LAT ophthalmic solution. During the second month (Period B), the mean IOP in the same eye was 9.8 ± 1.7 mm Hg (59 measurements) with treatment with a LAT and carteolol fixed combination (LCFC). And during the third month (Period C), the mean IOP was 7.4 ± 1.1 mm Hg (57 measurements) on the same right eye after the addition of brimonidine and brinzolamide fixed combination ophthalmic solution to the LCFC ophthalmic solution.
OUTCOMES
Comparisons of the IOPs between Periods A and B and between B and C showed that the reductions in the IOP were significant.
CONCLUSION
We conclude that frequent self-measurements of the IOP can determine that small changes of the IOPs are significant.
Topics: Male; Humans; Middle Aged; Intraocular Pressure; Low Tension Glaucoma; Glaucoma, Open-Angle; Antihypertensive Agents; Prostaglandins F, Synthetic; Latanoprost; Ophthalmic Solutions
PubMed: 36595993
DOI: 10.1097/MD.0000000000032478 -
Journal of Biosciences 2022Iron overload can induce oxidative stress, thereby inducing cell peroxidation. Arachidonic acid (ARA) is widely expressed in mammalian cells and esterified to membrane...
Iron overload can induce oxidative stress, thereby inducing cell peroxidation. Arachidonic acid (ARA) is widely expressed in mammalian cells and esterified to membrane phospholipids. To explore the effect of iron overload on the metabolism of membrane phospholipids MES23.5 cells were treated with various concentrations of ferric ammonium citrate (FAC) to induce oxidative stress. Using UHPLC (I-Class LC, Waters) coupled to a QTRAP (AB Sciex 5500) technology, the contents of 13 substances of ARA and its metabolites were detected. When the cells were given two different concentrations of FAC, we found that both high and low concentrations decrease the expression of ARA (p=0.002, p=0.02) compared with the control group. ARA has three metabolic pathways: the COX pathway, LOX pathway and CYP450 pathway. Compared with the control group, the LTB4 content in the LOX pathway was decreased (p=0.10) after treatment with lowconcentration FAC, while the LTB4 content was increased in the high-concentration treatment group (p=0.06). However, the content of 12S-HETE (p=0.23, p=0.05) in the LOX metabolic pathway decreased with increase of FAC concentration. Similarly, the content of 15S-HETE also decreased with increase of FAC concentration (p=0.17, p=0.02). The other downstream metabolites of ARA, 9S-HODE (p=0.54, p=0.18) and 13S-HODE (p=0.81, p=0.13) were not significantly changed. The contents of thromboxane B2 (TXB2), leukotriene D4 (LTD4), prostaglandin E2 (PGE2), 8-iso-prostaglandin F2α (8-iso-PGF2α), prostaglandin F2α (PGF2α), 6-keto-PGF1α, and prostaglandin D2 (PGD2) were too low to be detected in MES23.5 cells. The above results indicate that oxidative stress caused by iron overload reduces the LOX metabolic pathway of ARA.
Topics: Animals; Arachidonic Acid; Dinoprost; Leukotriene B4; Oxidative Stress; Iron Overload; Phospholipids; Hydroxyeicosatetraenoic Acids; Mammals
PubMed: 36550694
DOI: No ID Found -
Experimental and Molecular Pathology Feb 202317-trifluoromethylphenyl trinor prostaglandin F (17-CFPTPGF) was reported recently to exhibit in vitro and in vivo anticancer activity. Based solely on the results of in...
17-trifluoromethylphenyl trinor prostaglandin F (17-CFPTPGF) was reported recently to exhibit in vitro and in vivo anticancer activity. Based solely on the results of in silico molecular docking, it was claimed that this compound is NK1 receptor (NK1R) antagonist and that its activity is through this receptor. In this contribution we show that 17-CFPTPGF is only a very weak NK1R ligand (IC > 200 μM). In connection with that we discuss the issue of this compound's molecular target. Finally, we briefly narrate on the proper use of molecular docking in biomedical research.
Topics: Dinoprost; Receptors, Neurokinin-1; Ligands; Molecular Docking Simulation
PubMed: 36526011
DOI: 10.1016/j.yexmp.2022.104849 -
Journal of Sports Science & Medicine Dec 2022Dysmenorrhea with high prevalence has been categorized as primary dysmenorrhea (PD) and secondary dysmenorrhea due to differences in pathogenesis. A significant number... (Randomized Controlled Trial)
Randomized Controlled Trial
The Sprint-Interval Exercise Using a Spinning Bike Improves Physical Fitness and Ameliorates Primary Dysmenorrhea Symptoms Through Hormone and Inflammation Modulations: A Randomized Controlled Trial.
Dysmenorrhea with high prevalence has been categorized as primary dysmenorrhea (PD) and secondary dysmenorrhea due to differences in pathogenesis. A significant number of reproductive females suffering from monthly menstruation have to deal with negative impacts on their quality of life, work/study productivity, activities, and social relationships. In addition to medical treatment, exercise has been recognized as a complementary and alternative strategy for disease prevention, alleviation, and rehabilitation. This study aimed to investigate the potential effects of exercise on the severity of primary dysmenorrhea, physiological modulation, and physical fitness. Participants consisted of university students who were enrolled in the study and divided into a non-PD (Control) and a PD group based on recruiting criteria, the latter being randomly assigned to either an untreated dysmenorrhea group or a dysmenorrhea group that underwent 10 weeks of high intensity interval training (HIIT) exercise (Dysmen and DysmenHIIT, respectively). The DysmenHIIT group used spinning bikes and the training intensity was validated by heart rate monitors and BORG rating of perceived exertion. Forms containing participant information (premenstrual symptoms, menstrual distress, and a Short Form McGill Pain Questionnaire) as well as physical fitness, biochemical variables, hormone and prostaglandin (PGE2 and PGF2α) levels were assessed before and after the exercise intervention. After intervention, premenstrual symptoms (anger, anxiety, depression, activity level, fatigue, etc.), menstrual distress symptoms (cramps, aches, swelling, etc.), and pain severity were shown to be significantly mitigated, possibly through hormone (estradiol, prolactin, progesterone, and cortisol) modulation. Furthermore, high-sensitivity C-reactive protein (HsCRP), PGE2 and PGF2α levels were also down-regulated, resulting in the amelioration of uterine contraction and inflammation. Participants' physical fitness, including cardiovascular endurance and explosive force, was significantly improved after HIIT. The 10-week HIIT spinning bike exercise used in this study could be employed as a potential and complementary treatment for PD symptoms alleviation and considered as part of an educational health plan for promoting women's health. However, the effects of HIIT utilizing different exercise methods and accounting for different age populations and secondary PD warrant further investigation.
Topics: Humans; Female; Dysmenorrhea; Bicycling; Quality of Life; Dinoprost; Dinoprostone; Physical Fitness; Hormones; Inflammation
PubMed: 36523895
DOI: 10.52082/jssm.2022.595 -
Journal of Dairy Science Feb 2023This study was designed to evaluate whether the utilization of a second PGF treatment at the end of an estradiol/progesterone (E2/P4)-based protocol with or without GnRH...
Effects of additional gonadotropin-releasing hormone and prostaglandin F treatment to an estradiol/progesterone-based embryo transfer protocol for recipient lactating dairy cows.
This study was designed to evaluate whether the utilization of a second PGF treatment at the end of an estradiol/progesterone (E2/P4)-based protocol with or without GnRH at the beginning of the protocol would improve pregnancy rates of lactating Holstein cows assigned to timed embryo transfer. A total of 501 lactating Holstein cows in 5 farms were enrolled in the experiment. Within farm, cows were blocked by parity and, within block, were assigned randomly to (1) insertion of an intravaginal P4 device (controlled internal drug-releasing device; CIDR) and estradiol benzoate on d -11, PGF on d -4, CIDR withdrawal and an injection of estradiol cypionate on d -2, and timed embryo transfer on d 7 (1-PGF; n = 164); (2) the same treatments as 1-PGF, but with PGF administered on d -4 and -2 (2-PGF; n = 171); and (3) 2-PGF with the addition of a GnRH treatment on d -11 (GnRH2-PGF; n = 166). Ovaries were scanned by transrectal ultrasonography on d -11, -4, and 7, and blood samples were collected on d -11, -4, 0, and 7 for P4 determination. Treatment comparisons were performed using contrasts. The proportion of cows with a new corpus luteum on d -4 was greater in GnRH2-PGF cows. Cows in 1-PGF had a greater P4 concentration on d 0 but lesser P4 on d 7 compared with cows in the other groups. Cows assigned to receive 2-PGF (2-PGF and GnRH2-PGF) had greater estrus expression, and a greater proportion of cows ovulated to estradiol cypionate. No further contrast effects were observed for follicle diameter, double ovulation rate, pregnancy per embryo transfer (P/ET) on d 32 and 60, or pregnancy loss. As P4 concentration on d -4 increased, P/ET on d 60 tended to increase. Cows with P4 ≥3.66 ng/mL on d -4 had greater P/ET on d 32 and 60 than those with P4 below that threshold. Regardless of treatment, cows with P4 concentration ≥3.66 ng/mL also had a greater pregnancy per synchronized protocol (P/SP) on d 60. Also, a P4 concentration on d -4 (low or high) × follicle diameter (continuous) interaction tendency was observed when evaluating P/ET. Although P/ET did not differ among cows with different follicles sizes with reduced P4 concentration on d -4 (<3.66 ng/mL), it increased in cows with larger follicles exposed to increased P4 concentration (≥3.66 ng/mL). When P4 on d 0 was evaluated, P/ET on d 32 and 60 was greater for cows with low (≤0.09 ng/mL) versus high (>0.21 ng/mL) P4; as P4 concentration on d 0 increased, P/ET linearly decreased. In summary, cows with increased P4 concentrations during growth of the ovulatory follicular wave had improved P/ET. Administering a second PGF dose reduced P4 concentration on d 0 and increased ovulatory response to the protocol, but no benefits were observed on P/ET or P/SP.
Topics: Pregnancy; Female; Cattle; Animals; Gonadotropin-Releasing Hormone; Progesterone; Lactation; Dinoprost; Estrus Synchronization; Estradiol; Ovulation; Embryo Transfer; Insemination, Artificial
PubMed: 36460499
DOI: 10.3168/jds.2022-22134 -
Journal of Dairy Science Jan 2023Our objective was to evaluate the effect of 3 different Ovsynch protocols on progesterone (P4) and pregnancies per artificial insemination (P/AI), where all cows...
Effect of dose and frequency of prostaglandin F treatments during a 7-day Ovsynch protocol with an intravaginal progesterone releasing device on luteal regression and pregnancy outcomes in lactating Holstein cows.
Our objective was to evaluate the effect of 3 different Ovsynch protocols on progesterone (P4) and pregnancies per artificial insemination (P/AI), where all cows received a P4 releasing intravaginal device (PRID) from d 0 until d 8. We hypothesized that (1) both modified PGF treatments lead to decreased P4 at the second GnRH treatment (G2), resulting in greater P/AI, (2) the treatment effect is influenced by the presence of a corpus luteum (CL) at the beginning of the protocol, and (3) potential vaginal discharge caused by the PRID does not have a negative influence on fertility. Lactating Holstein cows (n = 1,056) were randomly assigned to 1 of 3 treatment groups on a weekly basis (n = 356; control: d 0, 100 µg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH). Cows in the second group (n = 353) received an Ovsynch protocol with a double dose of PGF (DoubleDose: d 0, 100 µg of GnRH + PRID; d 7, 50 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH). Cows in the third group (n = 347) received an Ovsynch protocol with a second PGF treatment 24 h after the first one (2PGF: d 0, 100 µg of GnRH + PRID; d 7, 25 of mg dinoprost; d 8, 25 mg of dinoprost and PRID removal; d 9, 100 µg of GnRH). All cows had their ovaries scanned to determine the presence of a CL at the beginning of the Ovsynch protocol. Vaginal discharge score (VS) was evaluated at PRID removal. All cows received timed artificial insemination approximately 16 h after G2. Pregnancy diagnosis was performed via transrectal ultrasonography (d 38 ± 3 after timed artificial insemination) and rechecked on d 80 ± 7 after timed artificial insemination. Blood samples were collected on d 0, 7, and 9 of the protocol to determine P4 concentrations. Treatment affected P4 at G2. Progesterone was lower for 2PGF and DoubleDose cows compared with cows in the control group (control 0.35 ± 0.02 ng/mL; DoubleDose 0.29 ± 0.02 ng/mL; 2PGF 0.30 ± 0.02 ng/mL). Overall, P/AI did not differ among treatments. We found, however, an interaction between treatment and CL at the first GnRH treatment. Cows lacking a CL at the first GnRH treatment in the 2PGF group had greater P/AI (47.9%) compared with the same type of cows in the DoubleDose group (32.7%). We observed an effect of VS on P4 concentration at d 7. We found an increase in P4 with greater VS. Vaginal discharge score at PRID removal tended to have a positive effect on P/AI at d 38 (VS0: 36.5%; VS1: 41.3%; VS2: 49.7%). In conclusion, the addition of a second PGF treatment on d 7 and 8 of a 7-d Ovsynch protocol increased luteal regression and decreased mean P4 at G2. Cows treated with PGF 2 times 24 h apart showed greater P/AI, compared with cows treated with an increased dose of PGF.
Topics: Pregnancy; Female; Cattle; Animals; Luteolysis; Progesterone; Dinoprost; Estrus Synchronization; Lactation; Pregnancy Outcome; Ovulation; Insemination, Artificial; Gonadotropin-Releasing Hormone; Vaginal Discharge; Cattle Diseases; Clinical Trials, Veterinary as Topic
PubMed: 36460496
DOI: 10.3168/jds.2022-22245