Uterotonic Activity Research Articles

Phytochemical constituents from the roots and lignotubers of Rhoicissus tridentata and their in vitro uterotonic activity

Rhoicissus tridentata is one of the most frequently used plants in preparing Isihlambezo, a herbal drink consumed by many South African women to induce labour and tone the uterus in pregnancy. This study aimed to identify the uteroactive compounds in this plant. Chromatographic purification of the methanol and water extracts from the roots yielded eight compounds, i.e. morin 3-O-α-L-rhamnopyranoside, trans-resveratrol 3-O-β-glucopyranoside, a mixture of asiatic and arjunolic acids, quercetin 3-O-rhamnopyranoside, catechin, β-sitosterol, and linoleic acid. All compounds were evaluated for their uterotonic effects using uterine smooth muscle isolated from stilboestrol-primed Sprague-Dawley rats. The mixture of asiatic and arjunolic acids showed the highest activity with EC50 of 0.02129 μg/mL for amplitude. These results validate the use of R. tridentata in ethnomedicine to facilitate labour in childbirth. Morin 3-O-α-L-rhamnopyranoside and trans-resveratrol 3-O-β-glucopyranoside caused a relaxation of the uterine muscle, which suggests that some compounds in R. tridentata possess opposing activities.

Утеротоническая активность препарата Рутоцин при применении высокопродуктивным свиноматкам в послеродовой период

Утеротоническая активность препарата Рутоцин при применении высокопродуктивным свиноматкам в послеродовой период

Transformation of Cloprostenol into E-Type Derivatives and a Comparative Study of Their Uterotonic Activity

Transformation of Cloprostenol into E-Type Derivatives and a Comparative Study of Their Uterotonic Activity

Evidence for carbetocin in obstetric hemorrhage

Introduction: a common procedure is to administer uterotonic agents regularly for the prophylaxis of postpartum and post-cesarean hemorrhage. The typical uterotonic drug recommended for this use is oxytocin, however, literature indicates better beneficial effects with carbetocin due to its sustained and prolonged uterotonic activity, as well as its safety and good tolerability. Objective: to outline the data on carbetocin that has been found so far in relation to obstetric hemorrhage. Methods: For this literature review, keywords related to carbetocin and obstetric hemorrhage were located using health sciences descriptors, and then searched in databases and search engines such as Google Scholar, PubMed, Lilacs, SciELO, Cochrane, and PubMed. Out of a total of 100 bibliographies, 32 articles were considered. Results: Carbetocin is a thermally stable drug with a half-life approximately 4-10 times longer than oxytocin, with sustained uterotonic activity with the administration of a single dose (100 μg) intravenously or intramuscularly. Conclusions: Carbetocin is a safe drug for prescription in patients with specific pathologies, as it maintains prolonged uterotonic effect, useful in post-cesarean hemorrhages. Its use is not yet fully promoted due to the high cost it represents at present

Prospects for the use of prostaglandin 11-deoxymisoprostol in obstetrics and gynecology: For medical abortion and the induction and initiation of labor (experimental work)

BACKGROUND: According to WHO (2015), abortion complications account for 8% of maternal deaths. These statistics have prompted the search for new ways to safely terminate early pregnancy. In 2010, at the World Congress of Obstetricians and Gynecologists in Lisbon, medical abortion was called a world revolution. Due to the introduction of medical abortion, maternal mortality after abortion decreased by 20,000 persons in 2012. Medical abortion using prostaglandin preparations, which can be used to solve this problem, is safer than surgical abortion, since curettage of the uterine cavity can cause inflammation, mechanical trauma, and infertility. In the Russian Federation, a prostaglandin preparation (misoprostol 200 mcg) has been certified for medical termination of pregnancy. However, this drug is expensive, as it is manufactured through complex chemical synthesis. At the Ufa Institute of Chemistry, Russian Academy of Sciences (UIC, RAS), due to a directed search for uterotonics among 11-deoxyprostaglandins of the E- and F-groups, a promising analog of prostaglandin E1 with a higher uterotonic activity than misoprostol was revealed. The agent is 11-deoxymisoprostol (11-DMP), which is several times cheaper and more accessible for synthesis.
 AIM: This study aimed to compare the pharmacological properties of misoprostol and 11-deoxymisoprostol.
 MATERIALS AND METHODS: The experiments were performed on non-linear white rats weighing 190210 g. The animals were fed with a standard diet for the entire experimental period. Animals were monitored and assessed on a daily basis. Animals were divided into six experimental groups, using their body weight as the main criterion for randomization (deviation of body weight values within the group was no more than 10%), with 20 animals in each experimental group. The drug was administered intragastrically at a dose of 10 mg/kg.
 To assess the immunotoxic properties, we studied the indicators of nonspecific and specific humoral immunity and cellular immunity in rats and assessed its effect on the mass of lymphoid organs and their cellularity. The allergenic properties of 11-DMP were evaluated using the methods of anaphylactic shock, indirect reaction of mast cell degranulation, reaction of immune complexes, and conjunctival test.
 RESULTS: After administration of 11-DMP, a decrease in the rate of weight gain, changes in behavior, and death of animals were not observed in any of the studied groups of males or females. The fertility index did not differ significantly in all experimental groups.
 The average number of fetuses per female, the sex ratio of rat pups, and the death rate of newborn rat pups did not change in the broods of all experimental groups.
 The study of the allergenic effect of the drug revealed that 11-DMP does not have allergenic properties, as shown by the reactions of mast cell degranulation, immune complexes, and the conjunctival test.
 CONCLUSIONS: When studying the pharmacological properties, it was revealed that 11-DMP compared with misoprostol has higher uterotonic properties; the therapeutic margin is 2 times greater, the toxicity is 2 times lower, and it is more stable and has a more accessible route of chemical synthesis.

In vitro uterotonic activities of cold aqueous stem bark extract of Erythrophleum suaveolens on estrogenized uterus of Nulliparous Guinea Pig

Medicinal plants have been used for different purposes. Interests in pharmacological and other scientific screening for the authentication of folkloric claims and drug development has become imperative. This study was aimed at investigating the effect of cold aqueous crude stem-bark extract of Erythrophleum suaveolens (CASBEEs) on estrogenized uterus of nonpregnant Guinea pig. Stem-bark of E. suaveolens were harvested, gently rinsed with clean water and dried under shade in a well-ventilated environment, ground into powder and cold aqueous crude extract of the processed plant material was obtained via maceration. Guinea pigs were estrogenized with 0.2 mg/kg diethylstilbestrol intraperitoneally 24 hours prior to in vitro drug administration. The uterine muscle of the animal was isolated and contractile responses were obtained using different graded volumes with CASBEEs (1 x 10-2 g/ml), oxytocin (1 x 10-4 g/ml), ergometrine (1 x 10-4 g/ml), and Acetylcholine (1 x 10-4 g/ml). The CASBEEs, caused contraction of the isolated estrogenized uterine muscles of the guinea pig in a dose-dependent manner. Maximum contraction (100%) for CASBEEs is at 0.6ml with a final bath concentration of 1.2 x 10-4 g/ml. comparatively, maximum contractile responses for the standard drugs was oxytocin 0.8 (1.6 x 10-6 g/ml) and ergometrine 0.8ml (1.6 x 10-6 g/ml) and Acetylcholine 0.4ml (8 x 10-7 g/ml). Aqueous crude extract of the stem-bark of Erythrophleum suaveolens exerted a dose-dependent and sustained uterotonic effect on estrogenized isolated uterine muscle of nulliparous Guinea pigs, thus authenticating the folkloric claim for its use to induce labour. Further studies on its mechanism of action and its use for fertility control should be explored.

Comparison of Oral Misoprostol with Intravenous Oxtocin in the Prevention of Primary Postpartum Haemorrhage in ESUT Teaching Hospital: A Randomized Controlled Trial

Background: Postpartum haemorrhage (PPH) is one of the major causes of maternal mortality globally. About 14 million patients suffer from postpartum haemorrhage annually worldwide, of which about 140,000 die. The active management of third stage of labour with the use of uterotonic drugs has reduced the risk of postpartum haemorrhage significantly. The most common uterotonic drug currently in use is oxytocin but the problem of insufficient skilled manpower for its administration, inadequacy of electric power supply to ensure the stability of the drug at appropriate temperature, and its high cost have made widespread use of oxytocin difficult in the resource-poor countries. This has made the search for an effective, affordable, stable and available alternative necessary. Misoprostol, an analogue of prostaglandin-E1, has a good uterotonic activity, is highly affordable, does not require specialized skill to administer and is very stable at room temperature. It also has multiple routes of administration, which makes its use in resource-poor countries indispensable. Aim: To determine if there is any difference in the efficacy of intravenous oxytocin over oral misoprostol in the prevention of primary postpartum haemorrhage. Study Design: This was a prospective, double-blinded, randomized study of uncomplicated pregnant women who had vaginal delivery in ESUT Teaching Hospital, Enugu. Sample Size: Two hundred (200) pregnant women who satisfied the inclusion criteria were recruited in this study with each arm of the study accommodating 100 participants. Methodology: The eligible women were recruited on presentation to the labour ward after giving their consent. They were randomly allocated into 2 groups: A and B. Group A received 2 tablets (400mcg) of oral misoprostol and 1mililtre (ml) of sterile water intravenously while group B received 2 tablets of white vitamin c and 1ml (10iu) of intravenous oxytocin immediately after cord clamping and cutting following the delivery of the baby. Pre-weighed delivery mats and vulval pads were used to collect the blood at delivery and for the first 24 hours for weighing and estimation of blood loss. A proforma was used to record the necessary data. Statistical Analysis: Data collected from the study was analyzed with the Statistical Package for Social Sciences (SPSS) computer software version 20.0 for windows. Statistical analysis was both descriptive and inferential at 95% confidence level. The socio-demographic variables were used to categorize the data and this was subjected to comparative statistical evaluation to yield frequencies, means, and percentages. Test of significance between class differences was by Pearson’s Chi-square test for categorical variables and student’s t-test for continuous variables. All P<0.05 at one degree of freedom (df=1) was considered statistically significant. Results: Two hundred pregnant women were recruited into the study with 100 women on each arm and all completed the study. The amounts of blood loss (in mililitre) in the misoprostol and oxytocin arms were 339.36 ± 122.28 and 378.52 ± 148.24, respectively. Forty-three women had PPH (blood loss ≥ 500ml) but there was no significant difference in the amount of blood loss and occurrence of PPH on both arms of the study. Conclusion: There was no difference in the efficacy of oxytocin over misoprostol in the management of the 3rd stage of labour for preventing PPH. We therefore, recommend that misoprostol can be adopted as an alternative/substitute to oxytocin in the management of the third stage of labour especially in the developing countries for prevention of PPH.

The uterotonic screening of calyx extracts of Hibiscus sabdariffa on estrogenized isolated Uterus of Wister strain albino rats

The claim of the use of orally consumed concentrated Hibiscus sabdariffa calyx preparation for the purpose of abortion in view of its widely uses as a beverage in the present period of economic hardship where it is a preferred beverage due to its affordability, naturalness and for its numerous medicinal properties has posed another element of concern to the female folks. This study was aimed to screen extracts of H. sabdariffa calyx of its acclaimed uterotonic activity. Contractile responses of estrogenized isolated rat uterus using various volumes (0.1, 0.2, 0.4, 0.6, 0.8, 1.0,1.6 ml) were established with oxytocin (1x10-4 g/ml), ergometrine (1x10-4 g/ml), misoprostol (1x10-4 g/ml), Acetylcholine (1x10-3 g/ml) and five different extracts of H. sabdariffa - ethanol (2.0x10-3 g/ml), methanol (2.0x10-3 g/ml), acetone (2.0x10-3 g/ml), cold water (2.0x10-3 g/ml) and hot water (2.0x10-3 g/ml). After these, nifedipine, acetylcholine and salbutamol were used to challenge the maximal responses of the isolated uterine tissue to oxytocin, acetylcholine and the cold aqueous extract of H. sabdariffa (CWEHs). The CWEHs was equally potent at inducing contraction activity compared to the standard drugs. This study further shows reduction in the amplitude of contraction produced by CWEHs in the presence of Promethazine (1×10−6 g/ml) and Nifedipine (1×10−6 g/ml). The blockade is more pronounced in promethazine compared to Nifedipine. Aqueous extract of Hibiscus sabdariffa calyx possess uterotonic activity on estrogenized isolated rat uterine muscle with mechanism of action related to histamine receptors and contraction of the myometrial cells as the was antagonized by promethazine and Nifedipine. This could be a justification for its alarming use as an abortifacient.

Evaluation of Uterotonic Activity, Acute Oral Toxicity, and Phytochemical Composition of Uvariodendron anisatum Verdc. Root Extracts.

Over 80% of cultural societies in low-income countries use plant preparations in traditional medicine with unknown potency and safety profiles. Uvariodendron anisatum root extracts are used by some Kenyan herbalists. However, the claims of the plant to remove retained placenta during birth have remained uninvestigated. Therefore, the current study evaluated its uterotonic activities. Acute toxicity in Wistar rats and the phytochemical composition of the plant were also studied. The plant was collected from Embu County in Kenya. The water and ethanol extracts were prepared by maceration. Uterine strips were isolated from primed mature female Wistar rats and used to study the uterotonic activities of the extracts. De Jalon's solution and oxytocin were used as negative and positive controls, respectively. Acute oral toxicity studies were done following the OECD 423 guideline and phytochemical screening were based on standard phytochemical procedures. The study met all the approval requirements before commencement. Data obtained from the uterotonic activity were analysed by using GraphPad Prism Version 8.0.1 software and expressed as a percentage increase or decrease of mean as mean ± SEM relative to the controls. The findings of acute oral toxicity were expressed using LD50. Additionally, the phytochemical components of the U. anisatum were tabulated. The uterotonic effect of Uvariodendron anisatum root water extract was higher than that of ethanol extract. A single dose of the Uvariodendron anisatum root water extract at 2000 mg/kg did not cause mortality in the tested Wistar rats. Besides, there were no changes in hematological and biochemical parameters. The extracts did not reveal changes in the gross morphology of the liver, kidney, heart, and lung of the tested Wistar rats. However, the histopathological studies of Uvariodendron anisatum root water extracts exhibited toxicity in the liver, kidney, and lung tissues of Wistar rats at a concentration of 2000 mg/kg. Alkaloids, glycosides, saponins, phytosterols, terpenes, proteins, phenols, and oils were recorded in Uvariodendron anisatum. The findings from this study provided scientific evidence which is useful in validating the use of Uvariodendron anisatum extracts in the stimulation of the uterus during birth.

In Vitro Uterotonic Activity of Launea taraxacifolia(wild) Fractions

IntroductionLaunea taraxacifolia(LT) is traditionally used by some native populations of Nigeria to ease labor pains and augment labor thereby facilitating childbirth. A previous study has reported the uterotonic property of the aqueous whole plant extract on isolated uterus of pregnant rats with activity involving oxytocin receptors. The aim of this study was to further validate this activity by evaluating the in‐vitrouterotonic effect of three different fractions of the plant on uterine strips of pregnant female Sprague‐Dawley rats in order to determine the most active fraction(s).MethodThe whole plant of Launea taraxacifolia plant was dried to constant weight and 45g sequentially fractionated using solvents of increasing polarity, i.e n‐Hexane, Ethyl acetate and Methanol. The percentage yield was calculated. The uterotonic property was investigated in vitro using rat uterine strips of rats in late pregnancy (Day18‐20 of gestation). Each pregnant rat was anaesthetized, the uterus removed, cleaned of the connective tissues and cut into strips of about 1 cm in length. Each strip was mounted in an organ bath of 25 ml capacity containing De Jalon physiological salt solution maintained at 37°C and continuously aerated with carbon dioxide and oxygen (5% carbon dioxide + 95% oxygen air mixture). The tissues were allowed to equilibrate for 30 min and normal myometrial contractions were recorded at baseline. Uterine contractile responses were elicited by adding oxytocin (0.17, 0.34, 0.68, 1.36 and 2.72 µg/ml), acetylcholine (4, 8, 16, 32, 64 µg/ml), n‐hexane, ethyl acetate and methanol fractions of LT (80, 160, 320, 640, 1280, 2560 and 5120 µg/ml) organ bath concentrations. Each concentration was allowed to act for 5 mins and the amplitude of contraction recorded by means of an isotonic transducer for three repeated experiments. Data were analyzed using Student t‐test. p<0.05 was considered significant. Dose‐response curves were plotted as displacement from baseline (cm) and percentage of maximal response against logarithm concentrations using Graph pad prism (version 8.3). The EC50 (i.e concentration causing 50% of maximal response) values were estimated by non‐linear curve fitting.ResultsThe methanol fraction gave the highest yield (3.37, 4.56 and 5.09%w/w for n‐hexane, ethyl acetate and methanol respectively). The methanol fraction showed a significant concentration dependent contraction of the uterine strips at 160, 320, 640, 1280, 2560 and 5120 µg/ml with the maximal response obtained at 1280 µg/ml (Figure 1). The n‐Hexane and ethyl acetate fractions did not produce contraction of the uterine strips but rather resulted in a relaxation of the uterine strips. On the other hand, oxytocin and acetylcholine produced a significant contraction at all the concentrations used. Furthermore, when compared to standard agonists, the EC50 obtained were 1270, 2144 and 17859 µg/ml for oxytocin, acetylcholine and LT methanol fraction respectively. The dose response curve of the percentage maximal response versus logarithm concentration was also shifted to the right (Figure 2).ConclusionThe methanol fraction of Launea taraxacifolia possess some uterotonic activity which are absent in the n‐Hexane and Ethyl acetate fractions. This suggests that the uterotonic compounds present in Launea taraxacifolia could be isolated from the methanol fraction.

Neurohypophyseal Peptides from Prague and Swedish Laboratories Used as Pharmaceuticals. Part 2: Desmopressin, Terlipressin, Carbetocin – Pharmacology and Clinical Applications

Licence agreements between the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague (IOCB), and the pharmaceutical company Ferring AB Malmö enabled the Swedish company to produce and commercialize worldwide a number of neurohypophyseal peptides designed at the IOCB. Several of them found therapeutic applications.
 dDAVP: 1-deamino-8-ᴅ-arginine-vasopressin was designed in one of the IOCB peptide laboratories (M. Zaoral and F. Šorm) in 1967. It displayed an extremely high antidiuretic activity (various tests indicate a 2- to 50-fold increase, as compared to arginine vasopressin) and a very low pressor activity. The peptide (covered by the U.S. Patent No. 3,497,491, 1970) has been used as a preferred drug in the substitution therapy of the central form of diabetes insipidus (Minirin®, today as Desmopressin INN). Besides, as later discovered (Mannucci et al. 1977), dDAVP increases the plasma concentration of the blood-clotting factor VIII. This fact extended its clinical use as haemostatics in cases of milder forms of haemophilia A, von Willebrand-Jürgens syndrome and some thrombocyte dysfunctions. Despite of the clinical success of dDAVP, a closer look reveals certain inadequacies in the presently available pharmacological data: several reports declare activity values and the prolongation effect (index of persistence) in very broad ranges.
 Triglycyl-8-lysine-vasopressin (Terlipressin), a peptide with lysine vasopressin chain extended at the N‑terminal by a triglycine residue, acts mainly as a prodrug (releasing lysine vasopressin after aminopeptidase splitting at the Nα group). The analogue belongs to the so-called „synthetic hormonogens“; individual peptides carrying various acylating groups were synthesized in the mid-sixties at the IOCB and legally protected by U.S. Patent No. 3,558,590 (1968). It was a part of the licence agreements mentioned above. The activities of triglycyl-8-lysine-vasopressin (both antidiuretic and vasopressor) are about 100 times lower than those of lysine vasopressin, but its persistence is 5 times longer. As such, it is occasionally used in emergency medicine in cases of esophageal (and other gastroenteral) bleeding, traumatic or septic shock, in cirrhotic patients and patients with portal hypertension. Its use as an early abortion drug was discussed but not pursued.
 Carbetocin (deaminocarba1-2-O-methyltyrosin-oxytocin) was synthetized in the laboratory of Karel Jošt at the IOCB before 1971; its synthesis was covered by a Czechoslovak patent (CS-149,028 B1) in June 1973 (at that time, Czechoslovak patent law did not provide for the patentability of substances as such) and first published in a biophysical communication by Frič et al., 1974). As a part of the licence agreement, it was included in the production program of Ferring AB, but marketed later also by several other pharmaceutical companies due to an incomplete patent protection. The peptide is a moderately active uterotonic partial agonist and as such has been utilized in veterinary obstetrics for delivery induction in cows and (multiparous) pigs: its milder and better-controlled uterotonic action was found preferential as compared to oxytocin so far used for these purposes. In the last two decades, carbetocin has been commonly used also in the human obstetrics, especially to prevent the peri- and post-partum haemorrhage, from the maternal side the most frequent and most severe delivery complication. It became a life-saving drug in emergency obstetrics.

Comparison of Oral Misoprostol with Intravenous Oxtocin in the In the Management of the Third Stage of Labour: A Randomized Controlled Trial

Background: Postpartum haemorrhage (PPH) is defined as the loss of 500ml of blood or more from the vagina following vaginal birth or 1000ml following caesarean delivery. The third stage of labour is the period between the delivery of the baby and the delivery of the placenta and membranes and its management is central to the prevention of postpartum haemorrhage (PPH). There are basically two methods of managing the third stage of labour namely active and physiological/expectant. The active management includes the use of uterotonic drugs immediately following delivery of the fetus, early cord clamping and cutting, and controlled umbilical cord traction. The active management of the third stage of labour with oxytocin has been found to reduce the risk of primary PPH significantly; however, the problem of inadequate supply of electricity, high cost and paucity of skilled manpower to administer it has negatively affected its use in developing countries and has made the search for a more suitable alternative expedient. Misoprostol on the other hand has been found to have good uterotonic activities, affordable and stable at room temperature; making its use in the resource-poor countries a veritable alternative. Aims: To determine if there is any difference in the efficacy of intravenous oxytocin over oral misoprostol in the management of the third stage of labour Study Design: This was a prospective, double-blinded, randomized trial of uncomplicated pregnant women who had vaginal delivery in the labour ward of the ESUT Teaching Hospital, Enugu. Sample Size: Two hundred (200) pregnant women who satisfied the inclusion criteria were recruited into the study with each arm accommodating 100 participants. Methodology: The eligible women were recruited on presentation to the labour ward after giving their consent. They were randomly allocated into 2 groups: A and B. Group A received 2 tablets (400µg) of oral misoprostol and 1mililtre(ml) of sterile water intravenously while group B received 2 tablets of white vitamin c and 1ml (10iu) of intravenous oxytocin immediately after cord clamping and cutting following the delivery of the baby. The patient was observed for significant clinical vaginal bleeding or PPH. For the purposes of this study, any bleeding/PPH accompanied with a greater than 30% rise in baseline pulse rate qualified for transfusion. A proforma was used to record the necessary data Statistical Analysis: Data collected from the study was analyzed with the Statistical Package for Social Sciences (SPSS) computer software version 20.0 for Windows. Statistical analysis was both descriptive and inferential at 95% confidence level. The socio-demographic variables were used to categorize the data and this was subjected to comparative statistical evaluation to yield frequencies, means, and percentages. Test of significance between class differences was by Pearson’s Chi-square test for categorical variables and student’s t-test for continuous variables. All P<0.05 at one degree of freedom (df=1) was considered statistically significant. Results and Conclusion: There was no significant difference in the number of women that received blood transfusion, the amount of blood transfused and the need for additional oxytocics on both arms of the study. However, there was a significant difference in the occurrence of side-effects with shivering and vomiting being prominent in the misoprostol and oxytocin arms respectively. Conclusion: There was no difference in the efficacy of oxytocin over misoprostol in the management of the 3rd stage of labour. We therefore, recommend that misoprostol can be adopted as an alternative/substitute to oxytocin in the management of the third stage of labour especially in developing countries.

Phytochemistry, traditional uses, and pharmacology of the genus Ekebergia (Meliaceae): A review

Ekebergia (Meliaceae) is a genus of flowering shrubs and trees widely distributed in the African continent. It is represented by four species namely E. capensis Sparrm, E. benguelensis Welw. ex C.DC, E. pterophylla (C.DC.) Hofmeyr and E. pumila I.M.Johnst. The information for this review has been collected via a survey performed through several online libraries including the Plantlist, Jstor, Scifinder, PubMed, Google Scholar, Web of Science and Dictionary of Natural Products. So far, about 69 distinct compounds have been isolated during the previous phytochemical studies of Ekebergia genus plants. These compounds belong to diverse classes of metabolites such as limonoids, triterpenoids, coumarins, steroids, alkaloids, stilbenes and phenolic compounds. Some of these isolates displayed various bioactivities including antiplasmodial, antimicrobial, antiproliferative or uterotonic activities. This review covers the traditional uses, the phytochemical and pharmacological investigations of the genus Ekebergia over the last four decades (1980 to 2020).

PENGARUH LILIN AROMATERAPI MINYAK LAVENDER (LAVANDULA ANGUSTIFOLIA) TERHADAP KONSENTRASI BELAJAR PADA SISWA MADRASAH TSANAWIYAH AL-WASHLIYAH PASAR MIRING DI DESA PASAR MIRING

Aromatherapy is an ancient healing process that uses pure aromatherapy plant extracts aimed at improving the health and well-being of the body, mind and spirit. Lavender contains linalil acetate and linalool. Linalil acetate and linalool have no harmful side effects on health. This substance is antibacterial, fungicidal, viriside, parasiticidal and vermifugal and has neurotonic and uterotonic action. This study aims to determine the effect of lavender oil (Lavandula angustifolia) aromatherapy candles on increasing the concentration of student learning at the Madrasah Tsanawiyah Al-Wasliyah Pasar Miring in Desa Pasar Miring . The study used a quasi-pretest-posttest experimental method for 30 randomly selected students. The instrument in this study used the Army Alpha Test with data analysis using Paired T-Test. Hypothesis testing using Paired T-Test showed p value = 0.026<0.05 (p <0.05). It can be concluded that there is an influence of lavender oil aromatherapy candles on increasing the concentration of student learning in Madrasah Tsanawiyah Al-Wasliyah Pasar Miring in Desa Pasar Miring

515 Repurposing of FDA-approved lead drugs as potentiators of uterine contractility in postpartum hemorrhage

Current medical options for management of postpartum hemorrhage preclude universal application due to their potential for adverse side effects. The objective of this study was to test the ex vivo efficacy of uterine-selective, FDA-approved drugs with no known cardiopulmonary toxicities repurposed for use at the human myometrial level. Lead drugs that selectively regulate human myometrial contractility were identified in prior studies using in vitro high throughput drug screening for calcium mobilization in myometrial cells. In this study, functional ex vivo isometric contractility was assessed via organ bath assays to determine uterotonic activity of mefloquine and pimavanserin on the human myometrial tissue. Human myometrial tissue was obtained at the time of cesarean delivery from non-laboring women meeting inclusion and exclusion criteria. Myometrial tissue strips (∼6-8 per biopsy) were submerged in organ baths (37°C, 95%O2, 5%CO2) containing Kreb’s Bicarbonate Solution and suspended under 3-gram isometric conditions. Tissues that displayed rhythmic spontaneous contractions were treated with cumulative concentrations (10pM – 0.1mM) of either mefloquine, pimavanserin or vehicle control (DMSO) at 20min intervals. Contractile activity was recorded and analyzed for frequency, amplitude, and area under the curve. Drug response relative to spontaneous contractile activity was analyzed, and non-linear regression models were used to generate concentration-response curves. Comparisons of fit were performed to determine if the non-linear curves of mefloquine and pimavanserin were significantly different (p<0.05) from DMSO. We performed 57 experiments in myometrial samples obtained from 12 women. There was no significant difference in the amplitude, frequency, or area under the curve between the vehicle control, mefloquine, and pimavanserin. Neither mefloquine nor pimavanserin induces ex vivo uterotonic activity in human myometrial tissue.

Evaluation of Ethyl Acetate, Chloroform and Toluene Fractions of &amp;lt;i&amp;gt;Thevetia peruviana&amp;lt;/i&amp;gt; (Pers.) K. Schum Methanolic Leaf Extract for Uterotonic Activity

<i>Thevetia peruviana</i> (Pers.) K. Schum (Apocynacae) leaves have a reputation of abortifacient activity. We investigated traditional claim and found that methanolic leaf extract produce antifertility activity by lowering the progesterone level in rat model. Aim of the present study was to find out the chemical constituent (s) responsible for antifertility activity of methanolic leaf extract of <i>Thevetia peruviana</i> (Pers.). The ethyl acetate, chloroform and toluene fractions of methanolic extract of <i>T. peruviana</i> leaves freed from cardiac glycosides [TPL-Me-G] were selected for phytochemical investigation and <i>in-vitro</i> uterotonic activity. The methanolic extract of <i>T. peruviana</i> leaves (1.103g) was fractionated with toluene (100ml, n=20); chloroform (100ml, n=20); and ethyl acetate (100ml, n=20) in the successive order. These fractions were examined for phytoconstituents and evaluated for <i>in-vitro</i> uterotonic activity. The toluene fraction (TPL-T) was found to have triterpenes, flavonoids and phytosterols. Quercetin (0.8904%) is present in TPL-T. The chloroform fraction (TPL-Ch) was found to contain flavonoids, triterpenes and phytosterols. Presence of alkaloids and flavonoids (quercetin 0.1606%) were observed in ethyl acetate fraction (TPL-Et-Ac). In contrast to TPL-Et-Ac, the TPL-T and TPL-Ch induced dose dependent uterine contraction in the isolated estrogenized rat uterus model. Highest uterotonic activity was found with TPL-Me-G which has kaempferol as phyto-constituent additionally. The <i>in-vitro</i> uterotonic activity is not influenced by quercetin and primary contributor is kaempferol though some unknown phytoconstituent/s also contributes to uterotonic activity and synergizes the action of kaempferol too. So, further research is needed to identify other contributory unknown phytoconstituent/s for antifertility activity of methanolic leaf extract of <i>Thevetia peruviana</i> (Pers.).

Misoprostol vs vasopressin as a single hemostatic agent in laparoscopic myomectomy: Comparable, or just better than nothing?

Laparoscopic myomectomy may be associated with considerable blood loss, especially in patients in whom no specific hemostatic measures are used. We conducted this retrospective comparative study to investigate whether misoprosol is an effective and safe alternative to vasopressin when used as single hemostatic agent in laparoscopic myomectomy. Two hundred cases undergoing laparoscopic myomectomy (-ies), were included. Of these, 50 pre-treated with vaginal misoprostol 400mcg 1 h before surgery (group 1), were compared with two historic consecutive groups: 100 patients treated with intraoperative intra-myometrial injection of dilute vasopressin (20 IU/100 mL normal saline) (group 2), and 50 treated without use of any hemostatic agent (group3). Mean procedure length did not differ significantly between the three groups (127.9 vs 100.6 vs 130.8 min). Mean estimated blood loss (EBL) was 179.7 ± 200.0 mL in group 1, compared with 147.8 ± 171.8 mL in group 2 (P = 0.793) and 321.8 ± 246.0 mL in group 3, respectively (P < 0.001). EBL was lower in group 2 in most of the study's subgroups of patients stratified according to size and number of fibroids compared with group 1, with the exception of patients with ≥4 fibroids, and ≥7 cm in size. In these subgroups, misoprostol appeared more effective. Neither agent was associated with serious adverse events. Vaginal misoprostol can be effective in reducing blood loss during laparoscopic myomectomy. Although rates of EBL are, in general, higher compared with those obtained with vasopressin, they are significantly reduced compared with those observed when no hemostatic agent is used. In extended procedures, vaginal misoprostol, due to its prolonged uterotonic action, may be associated with reduced blood loss compared with vasopressin.

An Updated Review: Adhatoda vasica

The present review mainly focuses on the morphological and pharmacological activities of the Adhatoda vasica belonging to the family Acanthaceae, which is commonly referred to as Adosa or Adsogi. It also focuses on the evidence based therapeutic uses of A.vasica in various experimental models. This plant is found in all the ecosystem in India and other parts of the world as well. Because of its greater availability and multitude of pharmacological activities, the plant is being used in the treatment of numerous diseases. Extracts of various parts of the plants such as bark, root, leaf, flower, fruit and many a times, the whole plants are used in the management of pain, inflammation, asthma, cold, cough, diabetes, bronchitis, diarrhea, dysentery and other upper respiratory diseases and it is also used to heal wounds; is utilised as an insecticide, and also used as abortifacient. In asthma and acute stages of bronchitis, the extract of vasica offers an unflagging result by decreasing the thickness of the sputum. Because of the above mentioned reasons the plant has greater importance in the various systems of medicines such as Ayurveda, Siddha, and Unani. According to the texts, the plant has greater power on asthma, abortifacient and uterotonic. Numerous trials have been conducted to prove the effects of A.vasica on asthma which led to its inclusion in WHO manual. According to the present day studies the alkaloids such as vasicinone, vasicine, and oxyvasicine which are present in A.vasica are responsible for most of the activities. But extensive studies need to be conducted to understand the constituent responsible for abortifacient and uterotonic activity.

The Uterotonic Screening of the Root Extract of Azanza garckeana (Malvaceae) on Isolated Wistar Rat Uterine Smooth Muscles.

Introduction Azanza garckeana (F.Hoffm.) Exell and Hillc. (family: Malvalceae) is traditionally used to induce or accelerate labour in pregnant women in Chongwe, Zambia, and the plant part which is commonly used are the roots. Aim The aim of this study was to screen Azanza garckeana crude extracts for uterotonic activity on isolated Wistar rat uterine smooth muscles. The likely mechanism of action for the plant extract was also investigated. Materials and Methods Fresh leaves and roots of the plant were collected and identified by a botanist at the University of Zambia. The methanol and cold root aqueous extracts were prepared by continuous maceration while the hot aqueous root extract was extracted using the Soxhlet method. The crude extracts of the plant were screened for uterotonic activity using uterine smooth muscles isolated from estrogenised adult nongravid female Wistar rats weighing between 160 g and 200 g. The activity of the plant was also evaluated in the presence of antagonists and tocolytic agents to determine the likely mechanism of action. Results The hot aqueous root crude extract (22.26%) had the highest yield followed by the cold aqueous (11.32%) and methanol extracts (6.26%), respectively. The methanol crude root extract demonstrated the highest potency (EC50 = 1.28 × 10−2 mg/ml; 95% CI 6.418 × 10−3 to 2.564 × 10−2; p=0.0001), while the cold aqueous extract was the most efficacious. Salbutamol and nifedipine significantly blocked the uterotonic activity of the extract. Conclusions This study provides scientific evidence on the uterotonic activity of Azanza garckeana with myometrial calcium mobilization as the possible mechanism of action.

Effect of the Ethanolic Extract of Gloriosa superba Linn (Langli) Roots on theReproductive System of Female Rats

Background The rhizome extract of Gloriosa superba Linn family Liliaceae is known to induce labor and facilitate normal delivery.Objective The present study was undertaken to assess the effect of ethanolic extract of Gloriosa superba Linn EyGS roots on the reproductive system of female Wistar rats.Material and Methods Immature ovariectomized OVX Wistar rats were administered EyGS orally at 20 and 40 mgkg body weight. Uterotrophic assay was performed to evaluate the effect of EyGS on estrogenic and progestogenic activity. The parameters evaluated were number of cornified cells in the vagina uterine weight and decidual weight. Biochemical parameters histopathology of the uterus and in vitro uterotonic activity were also assessed.Results Analysis of the effect of EyGS on vaginal cornification and deciduoma formation demonstrated vaginal opening without cornified cells decrease in uterine weight proliferation of uterus and reduction in deciduoma formation. EyGS produced decrease in the estrogen and progesterone levels and 80 contractions of the uterus compared to oxytocin.Conclusion The results indicate that the ethanolic extract of Gloriosa superba Linn had antiestrogenic and antiprogestogenic potential in OVX rats based on the physical histological and biochemical analyses. EyGS showed uterotonic activity in vitro and proves the folklore use of Gloriosa superba Linn.Keywords Gloriosa superba uterotrophic assay estrogenic vaginal cornification