PGF2 Research Articles

Effect of pseudopregnancy duration in nonpregnant sows on induced lactation.

This study was conducted to examine the effects of different pseudopregnancy periods in nonpregnant sows on artificial lactation induction efficiency and milk composition. Sixteen pseudopregnant sows (n = 4 per group) were treated with 5 mg of estradiol dipropionate at 28 (Group D38), 35 (Group D45), 42 (Group D52), and 49 (Group D59) days after the end of estrus, followed by prostaglandin F2α as 0.175-mg cloprostenol twice at 12 h intervals 10 days later. The overall success rate of lactation induction was 81.3%. The lactation rates were significantly higher in Groups D38, D45, and D59 (100.0%) than in Group D52 (25.0%). The milk immunoglobulin (Ig) G concentration was significantly higher in Group D38 than in Group D59. However, IgA levels and milk compositions (protein, ash, and lactose) did not differ among the groups. Lactation induction was successful between 38 and 59 days of pseudopregnancy. Apart from IgG, pseudopregnancy length did not affect milk components from 38 to 59 days of pseudopregnancy.

Understanding pregnancy-related hormones in female red pandas

Non-invasive techniques utilizing fecal samples to measure circulating steroid hormones have proven to effectively reflect the reproductive status of numerous species. Fecal progesterone metabolite (FPM) profiles have enhanced our understanding of the complicated reproductive strategies of many endangered species; however, this tool has been proven to not be optimal for pregnancy detection in the red panda (Ailurus fulgens). This study set out to investigate potential differences in FPM profiles (phases and lengths of hormone elevation) of seven female red pandas, both parturient and non-parturient, confirming FPM analysis is not a valuable indicator of pregnancy in this species. Secondly, examined whether a pregnancy related hormone, prostaglandin F2α and its metabolites (PGFM), can provide a reliable tool for confirming pregnancy in this species. Similarly, PGFM did not differentiate between parturient and non-parturient females until a significant peak the day of parturition (± 2 days). Interestingly, this is the first study to capture the PGFM surge associated with parturition, which may provide a tool for determining pregnancy in cases where live cubs were not observed.

PROTECTIVE ENVIRONMENTS FOR ANIMAL SPERM: EVOLUTION OF METHODS AND TOPICAL ASPECTS (REVIEW ARTICLE)

A retrospective review of domestic and foreign sources of literature is presented, as well as data of published own research on cryopreservation of animal sperm. The main historical stages of the creation of protective environments for deep freezing of sperm are given. In the 30s of the last century, a phenomenon characterized by the death of spermatozoa upon sharp cooling in the range of positive temperatures was discovered. It is called temperature shock of sperm. To prevent it, it is proposed to add substances containing phospholipids to the composition of diluents. Such environments can contain both simple components - native chicken egg yolk or milk, and high-tech - lipoproteins, isolated phospholipids of various origins. To stabilize protein-lipid complexes of plasma membranes and acrosomes of sperm during the cooling process, carbohydrates are added to the diluents. Sugars are components of energy supply for sperm and, along with salts, they are the main osmotic regulators. A combination of two or three carbohydrates in the medium was traditionally considered necessary. However, the Kharkiv school of reproductive specialists has proven the possibility of creating effective protective environments using only one sugar - sucrose or lactose - based on considerable practical experience. The effectiveness of germ cell freezing is shown depending on the cryoprotectants used. Glycerin is the first known endocellular cryoprotectant, which is still unsurpassed in sperm cryopreservation. Our own experimental data on the effect of combinations of glycerol with substances from the amide group on the main biological indicators of sperm after deconservation are presented. Cryoprotectants dimethylacetamide (DMAC) and dimethylformamide (DMF) were tested in own experiments on stallion semen. The experiments studied the effect of different concentrations of the above-mentioned penetrating cryoprotectants both on the main physiological characteristics of stallion sperm (motility, survival), and on the degree of damage to the membrane apparatus of sperm. The effectiveness of certain combinations of these substances has been proven. Methods of preventing the negative impact of oxygen and the development of lipid peroxidation processes in sperm during cryopreservation are presented. The concept of using additional hormonal components in diluents, in particular prostaglandin F2a, is revealed. The materials related to the effect on the quality of reproductive cells of healing preparations are displayed. Keywords: artificial insemination, environments, semen, animals, bulls, stallions, cryoprotectants, freezing.

Lysophosphatidic acid stimulates rat uterine contraction in vitro.

Lysophosphatidic acid (LPA) has been implicated in the uterine endometrial functions of implantation and decidualization; however, not much is known about its myometrial contractile function. Herein we characterized the uterotonic effects of LPA in non-pregnant (estrus) and peri-parturient rats in vitro. LPA dose-dependently (0.01-10 μM) stimulated the amplitude and integral, but not the frequency, of the uterine strip contraction of estrous rats. The stimulatory effect of LPA was enhanced 1 day before parturition but was lost 1 day postpartum. LPA did not cause the de novo synthesis of prostaglandin (PG) F2α but stimulated contractions cooperatively with the PG. LPA-induced contractions were significantly inhibited by an LPA1/2/3 antagonist in the uteri of estrous rats but not in term rats. This study characterized the uterotonic effect of a natural LPA that occurs at physiological concentrations, changes with reproductive states, and is independent of mediation by the newly synthesized PG.

Synchronization of estrus using progesterone injections followed by human menopausal gonadotropin in ewes.

Serial progesterone injections followed by human menopausal gonadotropin (hMG), instead of equine chorionic gonadotropin (eCG), were used to synchronize estrus in ewes. Shal ewes (n = 189) were assigned into five groups and each group was divided into two sub-groups to receive gonadotropins including eCG (300 IU; intra-muscular) or hMG (one ampoule; subcutaneously, SC). All ewes received prostaglandin (PG) F2α six days after introducing ram (day 0). Ewes received 0 (control), one, two, three or four injections of progesterone (50.00 mg; SC), 72 hr apart. The first progesterone was injected at the time of PG injection. Ewes in treatment groups received gonadotropins 48 hr after the last progesterone injection. Control group ewes received gonadotropins, at the time of PG injection. Mating was recorded after introducing fertile rams. Data were analyzed using GLM and GENMOD procedures in SAS. The incidence of estrus was less in control and ewes received a single progesterone (34.20%) compared to ewes received two (64.10%), three (81.10%) and four injections (68.40%) of progesterone. Time to estrus was earlier in control (45.70 ± 4.41 hr) than progesterone-treated groups (63.60 ± 1.79 hr). Fertility (51.30%) and fecundity (78.40%) of ewes received three progesterone injections were significantly greater than other progesterone-treated groups. There was no significant difference in reproductive indices between eCG and hMG sub-groups. In conclusion, during the non-breeding season, three injections of progesterone, three days apart, starting six days after ram exposure, in association with hMG, 48 hr after the last progesterone injection, could provide a sound reproductive performance in Shal ewes.

ТЕРАПЕВТИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ЭСТРОФАНТИНА ПРИ ПСЕВДОБЕРЕМЕННОСТИ (ГИДРОМЕТРЕ) У КОЗ

The aim of the study was to carry out a comparative evaluation of the therapeutic potency of Estrophantine®, a drug of the highly active synthetic analog of prostaglandin F2 alpha (PgF2α) cloprostenol, when goats with hydrometer were twice injected intramuscularly with a 10-day interval in a dose of 0.5 and 1.0 ml, respectively. The objects of the study were breeding goats of breeding age (n=6) and lactating goats (n=37) of the Zaanen breed diagnosed with false pregnancy during screening ultrasound examination. The animals were divided into two experimental groups according to the analogy principle. The animals in the first experimental group (n=21) were twice injected intramuscularly with a 10-day interval in the dose of 0.5 ml (125 μg cloprostenol), and those in the second group (n=22) were also twice injected intramuscularly with with a 10-day interval, but in the dose of 1.0 ml (250 μg cloprostenol). The results of the study showed high therapeutic potency of Estrophantine® when goats with hydrometer were twice injected intramuscularly with with a 10-day interval in the dose of 1.0 ml. After the first dose of the preparation complete expulsion of intrauterine fluid was noted in 81.82% of goats with hydrometer. The effectiveness of the method for a complete course of treatment was 100% according to the percentage of cured animals, and 86.36% and 77.27% according to the frequency of renewal of sexual cycling and pregnancy rate, respectively. None of the 5 (22.73%) goats found to be infertile registered a re-lapse of hydrometra after treatment. An Estrofantin® dose of 0.5 ml (125 μg cloprostenol) was found to be inadequate for treat-ment of goats with hydrometra. After the first dose, complete expulsion of intrauterine fluid was noted in only 52.38% of animals. When Estrophantine® is used at the lowest therapeutic dose (125 μg cloprostenol) the effectiveness of prostaglandin therapy over a full course of treatment is reduced by 4.76% in the proportion of cured animals, by 10.17% in the renewal of sexual cycling and by 15.37% in pregnancy rate. At the same time, the risk of relapse is 5%.

Approach to dysmenorrhoea in primary care.

Approach to dysmenorrhoea in primary care.

Effect of 2 Day vs. 3 Day Superstimulation Protocol on In Vivo Maturation of OPU derived oocytes in Buffaloes

The study was planned to evaluate effect of two different superstimulation protocols (2 Day vs. 3 Day) on in vivo maturation of oocytes in buffaloes. Buffaloes (n=8) were superstimulated twice using 2x2 design at an interval of 30-35 days using 200 mg and 300 mg FSH divided into four and six tapering doses (each dose of 50 mg) given over 2 and 3 days at 12 hourly intervals. Prostaglandin F2α analogue (500 μg Cloprostenol; i/m) at 72 and 84 hrs after start of superstimulatory treatment. Oocytes were retrieved from > 6 mm follicles at 48 h after the last FSH injection by ovum pick up. Oocyte maturation was assessed by the degree of cumulus cell expansion and by Orcein staining of denuded oocytes. OPU of 60 and 91 follicles resulted in recovery of 38 and 50 cumulus oocyte complexes (COCs) in 2-Day and 3-Day group, respectively. Significantly higher proportion of expanded oocytes was recovered in 3-Day protocol compared to 2-Day protocol (36.0% vs. 13.2%) and higher number of compact COCs were recovered in 2-Day protocol. In 3-Day protocol, significantly higher percentage of oocytes retrieved was at Metaphase-II stage compared to 2-Day protocol (40% vs.15.8%, respectively). The preliminary trial demonstrated that 3-day superstimulatory protocol yielded higher percentage of in vivo matured oocytes than 2-Day protocol in buffaloes.

Effects of intravaginal administration of prostaglandin F2α on luteolysis and subsequent estrus in Shiba goats (Capra hircus)

AbstractThis study examined the effects of intravaginal administration of prostaglandin F2α (PGF2α) on luteolysis and subsequent estrus in cycling goats. Goats with functional corpus lutea received one of five treatments: 2 mg of PG intramuscularly (IM2 × 1; n = 6), 2 mg of PGF2α intravaginally (IVG2 × 1; n = 7), 4 mg of PGF2α intravaginally (IVG4 × 1; n = 7), and 1 or 2 mg of PGF2α intravaginally 8 h apart (IVG1 × 2 group; n = 6 and IVG2 × 2; n = 8). Blood samples were collected at 24‐h intervals from 0 to 7 days after PGF2α administration. Estrus was checked twice daily during the experiment. The proportion of goats with complete luteolysis (reduction of progesterone concentrations to <1 ng/mL until 48 h after treatment) in the IVG2 × 1 group (28.6%) was significantly lower than in the other groups (IM2 × 1; 100%, IVG4 × 1; 57.1%, IVG1 × 2; 87.5%, IVG2 × 2; 100%, respectively). For goats completing luteolysis, there was no significant difference in the onset and duration of estrus among the groups. These results suggest that intravaginal administration of PGF2α can be applied as an alternative to intramuscular administration.

Trichostrongylosis: a zoonotic disease of small ruminants.

In the present world a significant threat to human health is posed by zoonotic diseases. Helminth parasites of ruminants are one of the most common zoonotic organisms on the planet. Among them, trichostrongylid nematodes of ruminants, found worldwide, parasitize humans in different parts of the world with varying rates of incidence, particularly among rural and tribal communities with poor hygiene, pastoral livelihood and poor access to health services. In the Trichostrongyloidea superfamily, Haemonchus contortus, Teladorsagia circumcincta, Marshallagia marshalli, Nematodirus abnormalis and Trichostrongylus spp. are zoonotic in nature. Species of the genus Trichostrongylus are the most prevalent gastrointestinal nematode parasites of ruminants that transmit to humans. This parasite is prevalent in pastoral communities around the world and causes gastrointestinal complications with hypereosinophilia which is typically treated with anthelmintic therapy. The scientific literature from 1938 to 2022 revealed the occasional incidence of trichostrongylosis throughout the world with abdominal complications and hypereosinophilia as the predominant manifestation in humans. The primary means of transmission of Trichostrongylus to humans was found to be close contact with small ruminants and food contaminated by their faeces. Studies revealed that conventional stool examination methods such as formalin-ethyl acetate concentration or Willi's technique combined with polymerase chain reaction-based approaches are important for the accurate diagnosis of human trichostrongylosis. This review further found that interleukin 33, immunoglobulin E, immunoglobulin G1, immunoglobulin G2, immunoglobulin M, histamine, leukotriene C4, 6-keto prostaglandin F1α, and thromboxane B2 are vital in the fight against Trichostrongylus infection with mast cells playing a key role. This review focuses on the prevalence, pathogenicity and immunological aspects of Trichostrongylus spp. in humans.

ADAMTS13 inhibits H2O2-induced human venous endothelial cell injury to attenuate deep-vein thrombosis by blocking the p38/ERK signaling pathway.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), a plasma metalloprotease that cleaves von Willebrand factor, acts as a critical regulator in normal hemostasis. This study was aimed to explore the role of ADAMTS13 in endothelial cell injury during DVT and the possible mechanism. First, human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2). Then, the mRNA and protein expressions of ADAMTS13 were evaluated with the reverse transcription-quantitative polymerase chain reaction and western blot. After treatment with recombinant ADAMTS13 (rADAMTS13; rA13), the viability and apoptosis of H2O2-induced HUVECs were assessed by cell counting kit-8 assay and terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining. In addition, the levels of prostaglandin F1-alpha, endothelin-1, and reactive oxygen species were detected using the enzyme-linked immunosorbent assay and dichloro-dihydro-fluorescein diacetate assay. The expressions of proteins related to p38/extracellular signal-regulated kinase (ERK) signaling pathway were estimated with the western blot. Then, p79350 (p38 agonist) was used to pretreat cells to analyze the regulatory effects of rA13 on p38/ERK signaling in H2O2-induced HUVEC injury. The results revealed that ADAMTS13 expression was significantly downregulated in H2O2-induced HUVECs. The reduced viability and increased apoptosis of HUVECs induced by H2O2 were revived by ADAMTS13. ADAMTS13 also suppressed the oxidative stress in HUVECs after H2O2 treatment. Besides, ADAMTS13 was found to block p38/ERK signaling pathway, and p79350 reversed the impacts of ADAMTS13 on the damage of HUVECs induced by H2O2. To sum up, ADAMTS13 could alleviate H2O2-induced HUVEC injury through the inhibition of p38/ERK signaling pathway.

Effect of Different Doses of Equine Chorionic Gonadotropini on Some Fertility Parameters in Zom Ewes Synchronized with Progesterone and Prostaglandin F2 Alfa during Breeding Season

Bu çalışma, Zom koyunlarında iki farklı dozda at koriyonik gonadotropini (equine chorionic gonadotropini; eCG) hormonu uygulamasının bazı fertilite parametreleri üzerine etkilerini incelemek için yapıldı. Bu amaçla, 77 baş Zom koyununa üreme mevsimi içerisinde 12 gün süreyle 20 mg fluorogestone acetate (FGA; progesterone analoğu) içeren vajinal sünger uygulandı. Koyunlar, süngerin çıkarılmasından 24 saat önce enjekte edilen eCG dozuna göre belirtildiği şekilde üç gruba ayrıldı; kontrol grubu (eCG enjekte edilemeyenler, n=30), eCG-400 (400 IU eCG enjekte edilenler, n=24) ve eCG-600 (600 IU eCG enjekte edilenler, n=23). Bu enjeksiyonla eş zamanlı olarak, tüm koyunlara 75 mcg kloprostenol (prostaglandinF2alfa (PGF2α); prostaglandin F2alfa analoğu) enjekte edildi. Tüm enjeksiyonlar kas içi yapıldı. Koyunların östrüsleri süngerin uzaklaştırılmasını izleyen 5 gün boyunca (günde 3 kez 30 dakika) arayıcı koçlarla kontrol edildi ve östrüste olduğu belirlenen koyunlar çiftleştirildi. Koyunların gebeliği çiftleştirme sonrası 60. günde ultrasonografi ile kontrol edildi. Kuzulayan koyunlar ve kuzuları doğumda kayıt edildi. Östrüs oranı, gebelik oranı, kuzulama oranı, çoklu kuzulama oranı, bir doğumdaki ortalama kuzu sayısı ve kuzu verimi açısından gruplar arasındaki farklılıklar önemli düzeyde olmadı (p>0.05). Bu sonuçlara göre, üreme sezonu içerisinde Zom koyunlarının östrüslerinin progesteron ve PGF2α kombinasyonuyla etkin olarak senkronize edilebileceği, ancak süngerin uzaklaştırılmasından 24 saat önce 400 veya 600 IU eCG uygulamasının incelenen döl verimi parametrelerine etkili olmadığı söylenebilir.

Prostaglandin F2α drives female pheromone signaling in cichlids, revealing a basis for evolutionary divergence in olfactory signaling

Pheromones play essential roles in reproduction in many species. Prostaglandin F2α (PGF2α) acts as a female reproductive hormone and as a sex pheromone in some species. An olfactory receptor (OR) for PGF2α was recently discovered in zebrafish, but this signaling pathway is evolutionarily labile. To understand the evolution of signals that attract males to fertile females, we used the African cichlid Astatotilapia burtoni and found that adult males strongly prefer fertile female odors. Injection of a prostaglandin synthesis inhibitor abolishes this attractivity of fertile females, indicating these hormones are necessary for pheromonal signaling. Unlike zebrafish, A. burtoni males are insensitive to PGF2α, but they do exhibit strong preference for females injected with PGF2α. This attractiveness is independent of the PGF2α hormonal receptor Ptgfr, indicating that this pheromone signaling derives from PGF2α metabolization into a yet-undiscovered pheromone. We further discovered that fish that are insensitive to PGF2α lack an ortholog for the OR Or114 that zebrafish use to detect PGF2α. These results indicate that PGF2α itself does not directly induce male preference in cichlids. Rather, it plays a vital role that primes females to become attractive via an alternative male OR.

Integrative transcriptomics and proteomics analyses to reveal the therapeutic effect and mechanism of Buxue Yimu Pills in medical-induced incomplete abortion rats

Ethnopharmacological relevanceMedical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. Aim of the studyThis study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. Materials and methodsExperimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. ResultsBYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. ConclusionBYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.

Presynchronization with simultaneous administration of GnRH and prostaglandin F2α (PGF2α) 7 days prior to Ovsynch improves reproductive profile in Hariana zebu cow

This study is aimed at assessing the impact of simultaneous administration of GnRH and prostaglandin F2α (PGF2α) 7days prior to Ovsynch in Hariana cow. Two hundred cyclic cows (> 4months postpartum) were assigned to control (n = 54) and pre-OV (n = 146). As per Ovsynch protocol, buserelin acetate (10μg), cloprostenol (500μg), and buserelin acetate (10μg) were injected i.m. on days 0, 7, and 9, respectively, in cows irrespective of treatment. But in pre-OV cows, buserelin acetate (10μg) and cloprostenol (500μg) were also injected i.m. simultaneously 7days prior to initiate the Ovsynch protocol. Artificial insemination was performed between 18 and 24h after the 2nd GnRH of Ovsynch in both treatments. Ultrasonography and blood sampling for hormonal analysis were done on each day of treatment, on day of AI, and 12days post-AI. Pre-OV treatment resulted to increased (45.20% vs 29.62%; P < 0.05) pregnancy outcomes and higher (P < 0.01) ovulation rate to first GnRH of Ovsynch than control. Cows showing complete luteolysis in response to PGF2α of Ovsynch were also higher (P < 0.05) in pre-OV than control. Greater (P < 0.05) synchronization rate was recorded in pre-OV than control (86.76% and 68.75%). The circulating concentrations of estradiol on day of AI and progesterone on day 12 post-AI were higher (P < 0.01) in cows diagnosed pregnant than non-pregnant in both control and pre-OV treatment. In conclusion, simultaneous administration of GnRH and PGF2α 7days before Ovsynch improved the synchronization rate and luteal profile in terms of CL area and hence resulted in higher conception rate in Hariana zebu cow.

Maternal exposure to PM2.5 induces cognitive impairment in offspring via cerebellar neuroinflammation and oxidative stress

Available evidence suggest that exposure to PM2.5 during pregnancy is associated with reduced cognitive function in offspring. This study aimed to investigate the effects of maternal exposure to PM2.5 on offspring cognitive function and to elucidate the underlying mechanisms. In this work, pregnant C57BL/6 female mice were exposed to concentrated ambient PM2.5 or filtered air from day 0.5 (=vaginal plug) to day 15.5 in the Shanghai Meteorological and Environmental Animal Exposure System, and offspring cerebellar tissues were collected on embryonic day 15.5, as well as postnatal days 0, 10 and 42. The mean PM2.5 concentrations exposed to the pregnant mice were 73.06 ± 4.90 μg/m3 and 11.15 ± 2.71 μg/m3 in the concentrated ambient PM2.5 and filtered air chambers, respectively. Maternal concentrated PM2.5 exposure was negatively correlated with offspring spatial memory significantly as assessed by the Morris water maze. Compared with the filtered air group, PM2.5-exposed offspring mice had reduced cerebellar microglia. Both RNA and protein levels of IL-8 and TNF-α were elevated in the concentrated ambient PM2.5 group. PM2.5 exposure increased the level of 8-OHG in miRNA of microglia and Purkinje cells in 6-week-old offspring. The level of prostaglandin F2α (8-iso-PGF2Aα) in the cerebellum was increased at different growing stages of offspring after gestational exposure of PM2.5. These results suggested that maternal air pollution exposure might cause inflammatory damage and oxidative stress to the cerebellum, contributing to reduced cognitive performance in mice offspring.

COMPARISON OF SUBLINGUAL MISOPROSTOL VERSUS INTRAVENOUS OXYTOCIN FOR REDUCING MEAN BLOOD LOSS AFTER VAGINAL DELIVERY

Postpartum hemorrhage (PPH) is significantly associated with maternal morbidity and mortality, and many maternal deaths are preventable. Uterine atony is managed through uterotonic agents like prostaglandin F2 alpha (PGF2a), misoprostol, ergometrine and oxytocin and uterine rubbing. This prospective study was designed to compare the role of sublingual misoprostol and IV oxytocin in preventing blood loss after vaginal deliveries. This study was conducted at the Department of Obstetrics &amp; Gynecology, Nishtar Hospital Multan, from 15 February 2021 to 14 August 2021. The study was conducted on 60 patients, 30 in both groups, who were selected through consecutive nonprobability sampling. Subjects were divided into Group A and Group B. 600 µg misoprostol (3 doses of 200 µg) was administered to Group A. 5 IU oxytocin was administered to Group B, with 3.3 IU/min at the beginning with the interval of 20 minutes until regular contractions are achieved. A maximum of 30mU/min oxytocin was infused. Mean blood loss was measured and recorded in proforma. The mean age of the subjects was 29.21 ± 6.07 years. The mean age of Group A was 29.40 ± 5.85 years, while that of Group B was 29.21 ± 6.32 years. Mean PPH blood loss in Group A, and B was 118.97 ± 20.26 ml and 154.13 ± 15.21 ml (P = 0.0001). The mean postpartum blood loss was higher by intravenous oxytocin than by sublingual misoprostol.

Docking is not enough: 17-trifluoromethylphenyl trinor PGF2α is only a very weak ligand of neurokinin-1 receptor

17-trifluoromethylphenyl trinor prostaglandin F2α (17-CF3PTPGF2α) 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-CF3PTPGF2α is only a very weak NK1R ligand (IC50 > 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.

PGF2α facilitates pathological retinal angiogenesis by modulating endothelial FOS-driven ELR+ CXC chemokine expression.

The pathological retinal angiogenesis often causes blindness. Current anti-angiogenic therapy for proliferative retinopathy targets the vascular endothelial growth factor (VEGF), but many patients do not radically benefit from this therapy. Herein, we report that circulating prostaglandin (PG) F2α metabolites were increased in type 2 diabetic patients with proliferative retinopathy, and the PGF2α receptor (Ptgfr) was upregulated in retinal endothelial cells (ECs) from a mouse model of oxygen-induced retinopathy (OIR). Further, disruption of the PTGFR receptor in ECs attenuated OIR in mice. PGF2α promoted the proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) via the release of ELR+ CXC chemokines, such as CXCL8 and CXCL2. Mechanistically, the PGF2α /PTGFR axis potentiated ELR+ CXC chemokine expression in HRMECs through the Gq /CAMK2G/p38/ELK-1/FOS pathway. Upregulated FOS-mediated ELR+ CXC chemokine expression was observed in retinal ECs from PDR patients. Moreover, treatment with PTGFR inhibitor lessened the development of OIR in mice in a CXCR2-dependent manner. Therefore, inhibition of PTGFR may represent a new avenue for the treatment of retinal neovascularization, particularly in PDR.

Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.

Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D2 (PGD2 ) and F2α (PGF2α ); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline-treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9. The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.