PGF2 Research Articles

SERUM DYNAMICS OF SOME REPRODUCTIVE HORMONES IN POSTPARTUM ANOESTRUS FRIESIAN X BUNAJI COWS TREATED WITH TWO DOSAGE REGIMENS OF OVSYNCH PROTOCOL

Fertility of the Post-partum period in dairy cattle is negatively influenced by the incidence of anoestrus. This condition is characterized by the absence of eostrus behaviour which may be due tophysiologic or pathologic factors. This study therefore, was aimed to compare the serum profiles of follicle stimulating hormorne (FSH), luteinising hormone (LH) and progesterone (P4) in response to the administration of two doses of gonadotrophin releasing hormone (GnRH, Lecirelin®) in combination with prostaglandin F2 alpha (PGF2α, Synchromate®) ovsynch protocol in apparently healthy, post-partum anestrous Friesian x Bunaji cows. Fifteen (n=15) animals were randomly divided into three groups and treated as follows: Group I (n=5) animals (control); Group II (n=5) animals received ovsynch 50 µg GnRH treatment; Group III (n=5) animals received 100 µg GnRH ovsynch treatment. Blood samples were collected at 15 to 30 minutes intervals for 6 hours to determine serum concentration of FSH and LH and once daily for 12 days after the injection of the first GnRH to determinate the concentration of plasma P4 using Enzyme linked immunosorbent assay kits. Peak values of FSH and LH were significantly (p<0.05) different on days 0 and 9.The plasma P4 levels increased among treated cows following injection of GnRH reaching a peak on day 7 compared to the control group. It was therefore concluded that the ovsynch protocol at the dosages indicated enhanced FSH, LH and P4 profiles compared to control cows and could initiate the onset of ovarian activity in the post-partum anoestrus Friesian x Bunaji cows.

M6A mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1

Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N6-methyladenosine (m6A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of m6A methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1. Using lipidomics, we identify prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as BAT-secreted insulin sensitizers. PGE2 and PGF2a inversely correlate with insulin sensitivity in humans and protect mice from high-fat-diet-induced insulin resistance by suppressing specific AKT phosphatases. Mechanistically, METTL14-mediated m6A promotes the decay of PTGES2 and CBR1, the genes encoding PGE2 and PGF2a biosynthesis enzymes, in brown adipocytes via YTHDF2/3. Consistently, BAT-specific knockdown of Ptges2 or Cbr1 reverses the insulin-sensitizing effects in M14KO mice. Overall, these findings reveal a novel biological mechanism through which m6A-dependent regulation of the BAT secretome regulates systemic insulin sensitivity.

Integrated metabolomics and lipidomics investigation of the mechanism of Danggui Sini Decoction on improving lipid homeostasis in primary dysmenorrhea

BackgroundDanggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. PurposeThe present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. MethodsDGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. ResultsDGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F2α (PGF2α)/PGE2, uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA2, LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. ConclusionOur findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.

Hormonal profiles and biomarkers leading to parturition in cattle.

This study aimed to understand the physiological mechanisms regulating parturition and to identify potential biomarkers to predict onset of birth. Additionally, we compared hormone profiles between cows with shorter and longer gestation lengths. Twenty-eight days before due date until 3d postpartum, cows (n = 18) were blood sampled daily. Circulating concentrations were measured for progesterone (P4) and estradiol (E2) by RIA, testosterone, prostaglandin F2α metabolite (PGFM), cortisol, pregnancy-specific protein B (PSPB) by ELISA and lactate concentrations by colorimetric assay. At end of gestation, P4 decreased from d-14 to d-4 (from 3.6 to 1.4ng/mL), most likely from rapid loss of placental P4 production (64% of decline in 24h). A second rapid decrease in P4 to undetectable concentrations was observed from d-2 to parturition (from 1.4 to 0.1ng/ml; most likely luteal origin) corresponding to increase in PGFM from d-2 to parturition (249.7 to 2868.4pg/mL). Estradiol and PSPB increased ~8-fold from ~13d before parturition with acute rise in E2 but not PSPB (45% vs 13% in first 24h). Testosterone decreased slightly during the same period. Cortisol and lactate increased only at calving. Comparison of cows with shorter vs longer gestation, when data were normalized to parturition day, a difference was detected in circulating E2 and PGFM patterns, but not P4 and PSPB. Thus, the first significant hormonal changes associated with parturition begin at d-14 with E2 and PSPB as two clear biomarkers of impending parturition. Cows with shorter and longer gestation had hormonal differences indicative of identifiable earlier placental maturation.

Comparative study between intralesional injection of prostaglandin F2α alone or combined with corticosteroids in the treatment of alopecia areata

Background Alopecia areata (AA) is an autoimmune disorder causing hair loss, yet its treatment remains challenging due to limited Food and Drug Administration approved therapies. Prostaglandin F2α (PGF2α) has emerged as a potential therapy. Objective To assess the efficacy of PGF2α intralesional injection in AA treatment. Patients and methods This case comparative work was performed on 75 localized AA patients who were split into three groups receiving different intralesional injections: group A received triamcinolone acetonide (TRA), group B received a combination of TRA and latanoprost (a PGF2α analog), and group C received latanoprost alone. Treatment response was assessed using the Severity of Alopecia Tool score, Severity of Alopecia Tool II, and Alopecia Areata Severity Index. Results High treatment response was observed in 76% of group B, compared to 64% in group A and 40% in group C. Group B showed the most significant reduction in severity score (median=0), followed by group A (median=1), and group C (median=3). Multivariate analysis identified group B as a significant predictor of a high treatment response (odds ratio=10.292, 95% confidence interval=1.904–55.632, P=0.007). Conclusion Intralesional injection of TRA and latanoprost (PGF2α analog) demonstrated superior efficacy in treating localized AA compared to other treatment modalities.

Effect of PG-600 dose in cows with persistent corpus luteum treated with PGF2α and hCG

The purpose of this study was to determine the effect of administering a dose of gonadotropin (PG-600) in cows with persistent corpus luteum (PCL) which were treated with prostaglandin F2 α (PGF2α) and human chorionic gonadotropin (hCG). This study used 20, three-year-old cows diagnosed with PCL, had recently given birth, and were not pregnant. Cows were randomly allocated into groups T0, T1, T2 and T3. Cows in all groups were injected with PGF2α (25 mg/cow). Simultaneously, cows in groups T1, T2 and T3 were also injected with PG-600 at doses of 100, 150 and 200 IU/cow respectively. PGF2α and PG-600 were injected when PCL was identified. After that, cows showing signs of estrus were injected with hCG (100 IU/cow) and artificially inseminated 12-18 hours after the appearance of signs of estrus. AI was conducted using frozen thawed semen. Sixty days following AI, a pregnancy examination was conducted using USG. Estrus was detected in all treated cows, while the pregnancy rates varied. Compared with other groups, the groups given 100 and 150 IU PG-600 produced higher pregnancy rates. It could be concluded that the combination of 25 mg PGF2α, 150 IU PG-600, and 100 IU hCG was the most effective treatment to produce high pregnancy rates in cows with persistent corpus luteum.

Combining the Vaginal Microbiome and Serum Metabolome to Screen for Potential Biomarkers of Early Pregnancy in Cows.

Early pregnancy diagnostic techniques are of significant importance in livestock farming, particularly in dairy farming. This study aimed to screen artificially inseminated cows for potential biomarkers at day 21 of pregnancy using microbiota-metabolomics analysis. The microbiome analysis revealed significant changes (p < 0.05) in the composition and abundance of the vaginal microbiota in cows after pregnancy. Notably, there was an increase in the abundance of [Eubacterium]_hallii_group (p < 0.05) associated with the production of short-chain fatty acids in the pregnant group compared with the non-pregnant group. Furthermore, significant alterations were observed in the serum metabolome, with notable changes in the concentrations of prolyl-hydroxyproline (Pro-Hyp) (p < 0.01) and bonactin (p < 0.01). The majority of differential metabolites clustered within the pathways of amino acid metabolism and lipid metabolism, with lipid metabolism exhibiting a higher proportion and playing a pivotal role in early pregnancy. An enzyme-linked immunosorbent assay was employed to quantify three key metabolites of the arachidonic acid pathway. The results demonstrated significant decreases in serum concentrations of leukotriene B4 (LTB4) (p < 0.05) and prostaglandin F2α (PGF2α) (p < 0.01) and no significant changes in arachidonic acid (AA) (NS) concentrations after 21 days of gestation in cows. Spearman's correlation analysis was utilized to investigate the interrelationship between the vaginal microbiota and serum metabolites. In conclusion, the present study demonstrated that biomaterials such as bonactin, Pro-hyp, LTB4, PGF2α in serum metabolites and [Eubacterium]_hallii_group in the vaginal flora of cows could be utilized as potential biomarkers for 21 days of gestation in cows.

Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage.

Cervical lymphatic vessels (cLVs) have been shown to drain solutes and cerebrospinal fluid (CSF) from the brain. However, their hydrodynamical properties have never been evaluated in vivo. Here, we developed two-photon optical imaging with particle tracking in vivo of CSF tracers (2P-OPTIC) in superficial and deep cLVs of mice, characterizing their flow and showing that the major driver is intrinsic pumping by contraction of the lymphatic vessel wall. Moreover, contraction frequency and flow velocity were reduced in aged mice, which coincided with a reduction in smooth muscle actin expression. Slowed flow in aged mice was rescued using topical application of prostaglandin F2α, a prostanoid that increases smooth muscle contractility, which restored lymphatic function in aged mice and enhanced central nervous system clearance. We show that cLVs are important regulators of CSF drainage and that restoring their function is an effective therapy for improving clearance in aging.

Fu's subcutaneous needling combined with monkshood cake-separated moxibustion for primary dysmenorrhea with cold congealing and blood stasis: a randomized controlled trial

To observe the clinical efficacy of Fu's subcutaneous needling combined with monkshood cake-separated moxibustion for primary dysmenorrhea with cold congealing and blood stasis. Sixty patients with primary dysmenorrhea of cold congealing and blood stasis were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 2 cases dropped out). The control group received monkshood cake-separated moxibustion at Shenque (CV 8) and bilateral Zigong (EX-CA 1), while the observation group received Fu's subcutaneous needling based on the control group. The muscles were palpated and the affected muscles were determined. Needles were inserted 5-10 cm away from the affected muscles and reperfusion activity was performed simultaneously. All the treatment started on the first day of menstrual cycle pain, once a day, for 3 days, totaling for 3 menstrual cycles. The visual analogue scale (VAS) score, Cox menstrual symptom scale (CMSS) score, and traditional Chinese medicine (TCM) syndrome score in the two groups were observed before treatment, after 2 treatment courses and after 3 treatment courses. The serum prostaglandin F2α(PGF2α) levels before and after 3 treatment courses were measured, and the clinical efficacy of the two groups was evaluated. After 2 and 3 treatment courses, the VAS scores, CMSS scores, and TCM syndrome scores in the two groups were lower than those before treatment (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05). After 3 treatment courses, the PGF2α level in the observation group was decreased (P<0.05), and were lower than that in the control group (P<0.05). The total effective rate was 96.6% (28/29) in the observation group, which was higher than 64.3% (18/28) in the control group (P<0.05). Fu's subcutaneous needling combined with monkshood cake-separated moxibustion could effectively reduce the pain intensity, improve clinical symptoms of dysmenorrhea, and lower PGF2α level in patients with primary dysmenorrhea of cold congealing and blood stasis.

Studies on in vivo antithrombotic activity of quercetin, a natural flavonoid isolated from a traditional medicinal plant, African eggplant (Solanum indicum)

Ethnopharmacological relevanceEvery year, cardiovascular diseases (CVDs) account for about 17.9 million deaths, making them the primary cause of both morbidity and mortality. Conventional drugs, which are often prescribed to treat cardiovascular diseases, are costly and have adverse effects. Consequently, dietary modifications and other medications are needed. Traditional use of Solanum indicum as cardiotonic to treat hypertension and anticoagulant potency has been reported but poorly evaluated scientifically. Aim of the studyThis study investigated the in vivo anticoagulant activity and mechanism of anticoagulation of quercetin (QC), a bioactive compound isolated from S. indicum (SI) hydroethanolic fruit extract. Materials and methodsBioassay-guided fractionation (anticoagulant activity) extracted QC from hydroethanolic SI extract. QC was extensively characterized biochemically and pharmacologically. The interaction between QC and thrombin was investigated using spectrofluorometric and isothermal calorimetric methods. Cytotoxicity, antiplatelet, and thrombolytic studies were carried out in vitro. The Swiss albino mice were used to assess the in vivo, anticoagulant, and antithrombotic activities of QC. ResultsQC exhibits anticoagulant activity via (i) uncompetitive inhibition of thrombin but not FXa with a Ki value of 33.11 ± 4.2 μM and (ii) a partial inhibition of thrombin-catalyzed platelet aggregation with an IC50 value of 13.2 ± 1.2 μM. The experimental validation of the in silico study's prediction of QC's binding to thrombin was confirmed by spectrofluorometric and isothermal calorimetric analyses. QC was nontoxic to mammalian, non-hemolytic cells and demonstrated thrombolytic activity by activating plasminogen. QC demonstrated in vivo anticoagulant efficacy, preventing k-carrageen-induced thrombus formation in mice's tails. In the acute circulatory stasis paradigm in mice, QC reduces thromboxane B2 (TXB2) and endothelin-1 (ET-1) while increasing nitric oxide synthase (eNOS) and 6-keto prostaglandin F1α (6-keto-PGF1 α). ConclusionEffective in vivo anticoagulant and antithrombotic properties of S. indicum's bioactive component QC point to the plant's potential use as a herbal anticoagulant medication for preventing and treating cardiovascular diseases linked to thrombosis.

A pheromone receptor in cichlid fish mediates attraction to females but inhibits male parental care

Reproductive behaviors differ across species, but the mechanisms that control variation in mating and parental care systems remain unclear. In many animal species, pheromones guide mating and parental care. However, it is not well understood how vertebrate pheromone signaling evolution can lead to new reproductive behavior strategies. In fishes, prostaglandin F2α (PGF2α) drives mating and reproductive pheromone signaling in fertile females, but this pheromonal activity appears restricted to specific lineages, and it remains unknown how a female fertility pheromone is sensed for most fish species. Here, we utilize single-cell transcriptomics and CRISPR gene editing in a cichlid fish model to identify and test the roles of key genes involved in olfactory sensing of reproductive cues. We find that a pheromone receptor, Or113a, detects fertile cichlid females and thereby promotes male attraction and mating behavior, sensing a ligand other than PGF2α. Furthermore, while cichlid fishes exhibit extensive parental care, for most species, care is provided solely by females. We find that males initiate mouthbrooding parental care if they have disrupted signaling in ciliated sensory neurons due to cnga2b mutation or if or113a is inactivated. Together, these results show that distinct mechanisms of pheromonal signaling drive reproductive behaviors across taxa. Additionally, these findings indicate that a single pheromone receptor has gained a novel role in behavior regulation, driving avoidance of paternal care among haplochromine cichlid fishes. Lastly, a sexually dimorphic, evolutionarily derived parental behavior is controlled by central circuits present in both sexes, while olfactory signals gate this behavior in a sex-specific manner.

Associations among the largest follicle, preovulatory estradiol concentrations, and predominant vaginal epithelial cells at the completion of hormonal ovarian stimulation for fixed-time artificial insemination in goats.

The objective of the present study was to investigate the association among the largest follicle (LF), preovulatory estradiol (E2), and predominant vaginal epithelial cell at the completion of hormonal ovarian stimulation for fixed-time artificial insemination (FTAI) in goats. Thirty-seven crossbred Boer does received gonadotropin-releasing hormone (GnRH) and intravaginal progesterone (P4)-releasing devices (day 0). On day 5, P4 devices were removed and does received prostaglandin F2α and equine chorionic gonadotrophin. On day 7, does received GnRH, and FTAI was undertaken. On day 7, does were divided into three groups, i.e. small-sized (3-3.9 mm; n = 5), medium-sized (4-4.9 mm; n = 8), and large-sized (≥5 mm; n = 24) according to the diameter of the ovarian LF; follicular characteristics (number and diameter) were identified, and blood samples and vaginal smears were collected. The average diameters of total antral follicles and LF and the percentage of superficial cell were greatest in large-sized LF does (p < .01). The average diameters of total antral follicle (r = .68) and LF (r = .71), number of preovulatory follicle (r = .58), and plasma E2 concentrations (r = .61) were positively correlated with the percentage of superficial cells (p < .01). The likelihood of a pregnancy outcome after the FTAI increased by 13.71 times in does with a greater average diameter of antral follicle, 14.18 times with emergence of a large preovulatory follicle, and 36.83 times with a higher percentage of vaginal superficial cells (p < .01). It was concluded that there is a relationship between the cell types of the vaginal epithelium, the diameters of the largest ovarian follicles, and the concentration of E2 in goats subjected to FTAI protocols.

Impact of Estrus Response and Pregnancy Rate of Two Cows That are Injected with Prostaglandin F2α Hormone in the System Maintenance is Different to Livestock Farming

Livestock farming is an effort to breed livestock to obtain benefits or results in the form of products and income. The success of a livestock business depends on three elements commonly referred to as the production triangle, namely seeds, feed, and management. In addition, the techno-socioeconomic characteristics of livestock farmers greatly influence the development of livestock businesses and will later affect the income of livestock farmers. The aim of the research was to examine the injection of the prostaglandin F2α hormone on the estrus response and pregnancy in Ongole crossbreed and Simental crossbreed cows reared using intensive and semi-intensive rearing systems. The data obtained will be analyzed using analysis of variance (ANOVA) and if there is a real effect, continue with further testing with Duncan's Multiple Range Test. The results of research on the percentage of estrus after the first and second injection of the prostaglandin hormone can be seen in the table. The highest percentage of estrus was in the S1P2 treatment with a percentage value of 80% and the lowest percentage value was in the S2P1 and S2P2 treatments with a percentage value of 40%. The percentage of estrus after the second injection, the percentage value for all treatments increased and the percentage of estrus was highest in the S1P2 treatment with a value of 100%. The average value of onset of estrus after the second injection of the PGF2α hormone was lower than the first injection. The longest duration of estrus in the treatment after the first PGF2α hormone injection was in the S1P2 treatment with an average of 24.75 hours, while the longest duration of estrus in the treatment after the second PGF2α hormone injection was in the S2P1 treatment with an average of 25 hours. PO cattle and Simental crossbreeds injected with PGF2α gave no different estrous responses. Intensive and semi-intensive rearing systems provide no different estrous responses. Raising PO cows using a semi-intensive rearing system injected with PGF2α provides an estrous response and high pregnancy rates (60), to be one of techniques to breed cattle of PO cow and have good impact to the success of a livestock business

PROGESTERONE PROFILES OF CROSS BRED SOWS FOLLOWING DOUBLE AND TRIPLE INJECTIONS OF DINOPROST TROMETHAMINE (LUTALYSE®) TREATMENTS

This study was carried out to evaluate progesterone profile of cross bred sows in Zaria following treatments with double and triple injections of Dinoprost tromethamine (Lutalyse®). Ten (n = 10) apparently healthy cross bred sows were randomly assigned to 2 treatment groups based on number of injections of Lutalyse®. Group 1 (n=5) received two injections of Lutalyse®(12.5mg) (days 0 and 13) while Group 2 (n=5) received three injections of Lutalyse®(12.5mg) (Day 0, 7, 13). Oestrus was monitored twice daily from 0700-1000 and 1500-1800h. Data on progesterone profile obtained during the oestrous cycle were expressed as mean ± SEM. Student t-test was used to compare the mean values between the groups. Graph pad Prism®data package for windows (2009) was employed for all statistical analyses. A value of P&lt;0.05 was considered significant. There was no statistical significant (P &gt; 0.05) difference in the overall mean serum P4 concentrations between groups 1 and 2. It is concluded that dinoprost tromethamine sodium can be used to synchronize sow oestrus, both double and triple injections of dinoprost tromethamine produces similar effect on progesterone concentration. It is recommended that double injections of dinoprost tromethamines hould be used for oestrus synchronization as no statistical significant (P&gt;0.05) differences were observed in the progesterone concentrations of both groups.

OESTRUS RESPONSES USING DOUBLE TREATMENTS OF PGF2a (LUTALYSE AND SYNCHROMATE) IN NIGERIAN JENNIES

This study was carried out to evaluate oestrus responses using double treatments of pgf2a (Lutalyse and Synchromate) in Nigerian jennies. Eight (8) cycling jennies aged 3.8 ± 2.0 years were used for this study. The jennies were randomly assigned to 2 groups of 4 jennies each; Group 1 (n=4): jennies treated with a double injection of 10mg of Lutalyse; Group 2 (n=4): jennies treated with double injection of 375μg of Synchroniate. Blood was collected from the jennies for extraction of serum, for progesterone and oestradiol estimation using Enzyme-Linked Immunosorbent Assays (ELISA). Groups 1 and 2, had time to onset of oestrus of 3.98 ± 0.95 and 1.78 ± 0.29 hours (P&gt;0.05), duration of oestrus of 78.0 ± 22.7 and 120 16.97 hours (P&lt;0.05), oestrus response rate of 75 and 100% and intensity of synchronization within 48 hours was 75 and 100% (P&lt;0.01), respectively. From this study it was established that the oestrus period and oestrus cycle length of groups 1 and 2 was 8 and 15 days and also 17 and 21 days, respectively, in Nigerian indigenous jennies. In conclusion, Synchronization of jennies is possible using exogenous PGF2a, however, double treatment of Cloprostenol Sodium (Synchromate) had a better response, therefore, it is more efficient than double treatment of Dinoprost tromethamine (Lutalyse) in oestrus synchronization of jennies.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma

BackgroundPrimary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer).MethodsThis was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18–75 years) with open-angle glaucoma or ocular hypertension.ResultsForty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55–8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61–8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events.ConclusionsLatanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life.Trial registrationThe study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

The Transcript Levels and the Serum Profile of Biomarkers Associated with Clinical Endometritis Susceptibility in Buffalo Cows.

Determining the gene expression and serum profile of the indicators linked to clinical endometritis susceptibility in Egyptian buffalo cows was the aim of this investigation. The buffalo cows that were enrolled were divided into two groups: forty infected buffalo cows with clinical endometritis and forty seemingly healthy buffalo cows that served as the control group. For the purposes of gene expression and biochemical analysis, ten milliliters of blood was obtained via jugular venipuncture from each buffalo cow. TLR4, IL-8, IL-17, NFKB, SLCA11A1, NCF4, Keap1, HMOX1, OXSR1, ST1P1, and SERP1 were manifestly expressed at much higher levels in the buffaloes with endometritis. On the other hand, the genes that encode SOD, CAT, NDUFS6, Nrf2, and PRDX2 were down-regulated. There was a significant (p < 0.05) elevation of the serum levels of non-esterified fatty acids (NEFAs), beta hydroxy butyric acid (BHBA), triglycerides (TGs), globulin, creatinine, and cortisol, along with a reduction in the serum levels of glucose, cholesterol, total protein albumin, urea, estrogen (E2), progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroxine (T4), prostaglandin F2 α (PGF2α), calcium, iron, and selenium, in the endometritis group in comparison with the control. However, no significant change was observed in the values of phosphorus, magnesium, copper, or zinc in either group. Within the selective breeding of naturally resistant animals, the variation in the genes under study and the changes in the serum profiles of the indicators under investigation may serve as a reference guide for reducing endometritis in Egyptian buffalo cows.

TREATMENT OF CLINICAL ANOESTRUS IN ARABIAN MARES BY A PROSTAGLANDIN F2 α|ή‎|‎ωϧΔΔ ‎‎|‎ ‎

A synthetic prostaglandin F2 α(PGF2 α) analogue, luprostiol* , was used in treatment of clinically anoestrus Arabian mares that suffered from abnormal persisting luteal function. Thirty two anoestrus mares were selected for this study after careful examination of their breeding history and a thorough genital examination which included rectal palpation of the genital tract and ovaries. The genital examination also included a vaginoscopy of the vagina and cervix. These mares were diagnosed as clinically anoestrus during the spring and summer months breeding season and received a single intramuscular injection of the prostaglandin F2 α. Twenty six mares (81%) responded to the treatment and came to oestrus within 2-4 days. Ovarian activity of the induced oestrus was monitored by rectal palpation and the mares were bred twice according to their follicular development. A total of 13 mares (54%) became pregnant as a result of the treatment and pregnancies were confirmed later by rectal palpation. This study reveals that the majority of non-cycling mares during the spring and summer months breeding season are in a prolonged luteal function rather than inactive ovaries or ‘true anoestrus. The study also demonstrates the efficiency of Iuprostiol in the treatment of clinically anoestrus mares.

Blood Sampling and Hormone Measurement for Determining the Stage in the Ovarian Cycle in Marmosets.

Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.

Untargeted Metabolomics of the Sea Cucumber, Bohadschia marmorata (Jaeger, 1833)

The marine invertebrates such as sea cucumber are regarded as sources of diverse bioactive compounds with promising health and nutritional benefits. Many commercially traded sea cucumber species have been explored, yet none of the local low-value types in the province of La Union, Philippines. This study aimed to establish a baseline metabolomic profile of Bohadschia marmorata (Jaeger, 1833). The identification of compounds in its body wall utilized an Orbitrap MS-based approach. Metabolites were annotated using Compound Discover 3.2, and similarity searches were performed from online databases. Eleven putatively identified compounds, which included saponin (3beta,5xi,9xi)-28-Hydroxy-28-oxoolean-12-en-3-yl-beta-Dgalac topyranosyl-(1-3)-[beta-D-glucopyranosyl-(1-2)]-beta-D-glucopyranosiduronic acid, fatty acids and their byproducts such as eicosanoid (11,12-Epoxy-(5Z,8Z,11Z)-icosatrienoic acid) and prostanoids (13,14-dihydro Prostaglandin F1?; 13,14-Dihydro-15-keto Prostaglandin A2), dicarboxylic acids (tetradecanedioic acid; dodecanedioic acid; suberic acid; NP-001596), and amino acid (4-Oxoproline). The metabolic profile of the B. marmorata body wall showed a diverse group of representative metabolites common among holothurians associated with innate defense mechanisms, structural composition, and products of metabolic pathways. There is, however, a need to further isolate these compounds using other methods and test their biological activities.