Effect of 17-alpha-hydroxy-progesterone capronate on the motility of the human uterus in puerperium following abortion

The effects of 17alpha-hydroxyprogesterone capronate (17-OH-P) on spontaneous uterine motility and on oxytocin-induced uterine contraction during the postabortion period were studied in 22 women. The effects of 17-OH-P were present 8 hours after administration and still appreciable after 12 hours, but were considerably diminished after 24 and 48 hours. The efficiency of 17-OH-P in inhibiting uterine contraction after administration of oxytocin is clearly inferior to that of natural progesterone.     

Uterokinetic activity of fenprostalene (a prostaglandin F2alpha analog) in vivo and in vitro in the bovine

The luteolytic potency of fenprostalene (a PGF2alpha analog) is about 20-times that of naturally produced PGF2alpha. The objective of this research was to investigate the uterokinetic effects of fenprostalene at a luteolytic dosage (1.0 mg) in the cyclic and early postpartum cow, and in the isolated uterine horn. Uterine motility measurements were conducted on two consecutive days in each cow. Experimental protocol on Day 1 was: spontaneous motility was recorded for 1 h; fenprostalene was injected (1.0 mg i.m.), after which motility was recorded for 2 h; fenprostalene was injected (1.0 mg i.v.) and motility was recorded for 30 min; and oxytocin was injected (40 U i.v.), followed by a 30-min recording period. On Day 2, the treatment sequence was reversed: spontaneous motility was recorded for 1 h; oxytocin was injected (100 U i.m.), after which motility was recorded for 2 h; fenprostalene was injected (1.0 mg i.v.) and motility recorded for 30 min; and oxytocin was injected (40 U i.v.), followed by a 30-min recording period. In the in vitro experiment, different dosages of fenprostalene (5.9, 11.8, 17.6, and 29.4 ng/ml bath solutions) and oxytocin (0.06, 0.12, 0.18, and 0.60 mU/ml bath solutions) were tested in pairs for 1 h. The treatment was then repeated. In a different group, fenprostalene (5.9 ng/ml bath solution) and oxytocin (0.06 mU/ml bath solution) treatments were alternated. Fenprostalene (at luteolytic dosage) was not uterokinetic in either the cyclic or postpartum cow. However, fenprostalene and oxytocin had a significant uterokinetic effect (five- to six-fold pretreatment value) on the isolated uterine horn preparation at all dosages studied. Peak motility occurred between 10 to 15 min, followed by a gradual decrease to 40% at 60 min. When the treatments were repeated at 60 min, oxytocin but not fenprostalene caused a minute, transient contraction. However, fenprostalene-desensitized (by exposure to fenprostalene) uteri reacted significantly to oxytocin, and vice versa.     

Effect of different doses of prostaglandin E2 on intrauterine pressure and uterine motility during diestrus in experimental cows

Studies in human medicine proved the important role of prostaglandin E2, which stimulates uterine contractions in vivo and in vitro and has been extensively used to ripen the cervix around labor. We wanted to demonstrate that increasing the dosage of prostaglandin E2 (1.25 mg, 2.5 mg, 5 mg and 10 mg) provokes an increase in intrauterine pressure and uterine motility in cattle. Five healthy, lactating dairy cows were used as experimental animals for this study. Intrauterine pressure was recorded during the diestrus phase (1 recording per cow and diestrus phase) by means of a transcervically placed intraluminal pressure microtransducer. Physiologic uterine motility was recorded for 30 min, then placebo or one of the prostaglandin E2- dosages was administered through an indwelling catheter in the jugular vein, followed by a 2-h recording period (eight 15-min periods). Area under the curve (AUC), mean amplitude, frequency of pressure waves and intrauterine pressure were analyzed. Furthermore, we recorded protocols for monitoring heart and respiratory rates and side effects at 9 given examination times. Significant differences were found for the AUC, the mean amplitude and the intrauterine pressure (P < or = 0.05), whereas the number of pressure waves per 15 min did not differ significantly among treatments. Peak values for AUC, mean amplitude and intrauterine pressure were found during the first 15 min after administration of 10 mg of prostaglandin E2. Dose-effect curves showed that the 2.5 mg dosage provided the optimal ratio between myometrial stimulation and undesirable side-effects.     

The inhibitory mechanism of GLP-1, but not glucagon, on fasted gut motility is dependent on the L-arginine/nitric oxide pathway

Effects of glucagon-like peptide-1 (GLP-1) and glucagon on fasted gut motility in conscious rats were investigated as regards dependence on nitric oxide (NO). Small bowel motility was studied by electromyography and a jugular vein catheter was implanted for administration of drugs. GLP-1 (5-40 pmol x kg(-1) x min(-1)) prolonged the cycle length and abolished phase III of the migrating myoelectric complex (MMC) (P<0.01). Low doses of GLP-1 did not affect duration, propagation velocity or calculated length of phase III. At 1 mg x kg(-1) N(omega)-nitro-L-arginine (L-NNA) blocked the GLP-1 response up to a dose of 10 pmol x kg(-1) x min(-1) (P<0.05), while higher doses were able to overcome L-NNA-induced disinhibition of the GLP-1 response (P<0.05). Similarly, L-arginine at 300 mg x kg(-1) prevented L-NNA-induced disinhibition of the GLP-1 response (P<0.05). Glucagon (200-1000 pmol x kg(-1) x min(-1)) prolonged the cycle length and abolished phase III of MMC (P<0.01) independent of NO. Again, low doses of glucagon did not affect duration, propagation velocity or calculated length of phase III. In conclusion, inhibition of fasted motility by GLP-1 at low doses is dependent on NO, while high doses of GLP-1 and glucagon exert effects on motility independently from NO.     

Effects of epidural administration of xylazine or lidocaine on bovine uterine motility and perineal analgesia

The objective of this study was to evaluate and compare the effects of caudal epidural (sacral-coccygeal interspace) administration of xylazine or lidocaine on uterine motility and perineal analgesia in the cow. Six Holstein cows (7 d post estrus) were assigned to one of three treatment groups: control (5 ml saline); lidocaine (0.2 mg/kg, 2% solution); and xylazine (0.06 mg/kg suspended in 5 ml saline), with each cow randomly assigned to each treatment over a period of three estrous cycles. Uterine motility, perineal analgesia, electrocardiography, and overt signs of sedation were recorded. Data were collected at 10-min intervals starting 10 min before treatment and continuing until 60 min post treatment. At 60 min post treatment, oxytocin (20 USP units) was administered i.v. to serve as a positive control for uterine motility. In the xylazine group, uterine motility significantly (P < 0.05) increased at 20 min post treatment, peaked at 30 min, and gradually decreased to non-significant levels at 50 min post treatment when compared with the lidocaine and control groups. Additionally, xylazine produced a higher degree and longer duration of perineal analgesia than lidocaine. Systemically, epidural xylazine produced signs of sedation, salivation, vocalization and bradycardia. Ataxia was also observed in the xylazine-treated group which may have been induced through a local and/or systemic effect. The individual properties of xylazine and lidocaine should be taken into consideration when performing an obstetrical procedure requiring the use of an epidural analgesic agent, and they should be utilized to benefit the clinician in performing the procedure.     

Comparative effects of 6-hydroxydopamine and alpha-adrenoceptor antagonists on intrauterine migration and spacing of blastocysts in the rat

Sympathetic nerve terminals were destroyed by administration of 6-hydroxydopamine (2 x 50 mg/kg) at 10:00 h on Days 4 and 5 of pregnancy in the rat. In the myometrium, this treatment markedly decreased noradrenaline concentrations (by 99%, P less than 0.001), demonstrating that myometrial noradrenaline is mainly originated from sympathetic nerves; therefore after 6-hydroxydopamine, the distribution and spacing of blastocysts remain unaffected throughout the uterus. Administration of phenoxybenzamine (2 x 6 mg/kg) in the morning of Days 4 and 5, or prazosin (4 x 3 mg/kg) from 12:00 h on Day 4 until 12:00 h on Day 5 disorganized the even distribution of blastocysts from the tubal end to the cervical end of the uterine horns. These results provide evidence that a noradrenergic transmission via action on myometrial post-synaptic alpha 1-adrenoceptors is involved as a regulatory mechanism of uterine motility for distribution and spacing of blastocysts in the rat uterus.     

Effects of the acute and chronic administration of chlordiazepoxide on the development of spontaneous motility in chick embryos

The effects of the acute and chronic administration of chlordiazepoxide on spontaneous motility and on the reactivity of the generator of embryonic motility were studied in chick embryos from the 4th to the 19th day of incubation. 1. The acute administration of chlordiazepoxide (5 mg/kg e.w.) significantly depressed spontaneous motility from the 13th day of incubation. 2. The chronic administration of chlordiazepoxide (12.2 mg/kg e.w./24 h) from the 4th to the 8th, 12th and 16th day of incubation enhanced the reduction of the spontaneous motility of 17-day-old embryos. 3. The chronic administration of chlordiazepoxide significantly modified the activity of both activators (strychnine, metrazol, bicuculline, picrotoxin) and inhibitors (GABA, chlordiazepoxide) of the spontaneous motility of chick embryos.     

Plasma levels of cortisol and oxytocin,and uterine activity after cervical artificial insemination in the ewe

The objective was to compare in the ewe the effects of easy and difficult procedures for artificial insemination (AI) (as related to rapid or poor accessibility of the cervix, respectively) on plasma cortisol (CORT) and oxytocin (OT), and uterine motility. All AI were simulated using a catheter empty of semen to study genital and environmental stimuli only. In experiment 1, 40 ewes were sampled after Al, and whether it was an easy or difficult procedure was reported for each animal. While CORT concentrations rose to a similar amount in all ewes, whatever the Al procedure, a significant OT response occurred after a difficult procedure only (n = 18) (17.4 +/- 1.7 versus 12.7 +/- 0.7 pg x mL(-1) before Al, p < 0.05). In experiment 2, uterine activity was monitored in 4 ewes using an implantable telemetric transmitter equipped with an intrauterine pressure catheter. An increased uterine activity occurred during 2 +/- 1 min after an easy Al (n = 5), whereas the evoked activity lasted for 15 +/- 4 min after a difficult Al (p < 0.001, n = 7). A similar long-lasting response occurred after OT administration (100 mIU, i.v.). We concluded that the increase in uterine motility after a difficult Al resulted from a reflex release of OT, and not to a "stress" effect.     

Development of spontaneous motility in chick embryos. Further components of aminergic mechanisms

The participation of central monoaminergic systems in the regulation of spontaneous motility in developing chick embryos was tested by systemic administration of several drugs, which affect the different sites of central aminergic systems. Amphetamine (2 mg.kg-1 egg weight) evoked an age-dependent depression of spontaneous motility, which first occurred in a significant fashion on day 13 of incubation. Two thirds of this depression depended upon supraspinal influences. The effect of p-chlorophenylalanine (100 mg.kg-1 e.w.) consisted from day 15 of incubation in a short-lasting depression followed by partial recovery of resting motility. alpha-methyldopa (100 mg.kg-1 e.w.) depressed the spontaneous motility from day 13 of incubation, without any signs of recovery within the first hour after drug administration. The most pronounced depressive effect was evoked by melatonin (25 mg.kg-1 e.w.) even in 11-day-old embryos. Along with the increased depth of depression the recovery of motility declined until full cessation of motility was achieved in 17-day-old embryos. The results were interpreted as constituting further evidence for the involvement of central aminergic systems in the development of supraspinal control over spontaneous motor activity generated by the CNS.     

Use of pyridoxine hydrochloride in the interruption of lactation in female dogs with pseudopregnancy

The aim of this research was to evaluate the use of pyridoxine hydrochloride and its associated side effects in the treatment of pseudopregnancy in female dogs. A total of 40 female dogs, with no defined breed, in non-gestational diestrus, with clinical complaint of milk production were selected. The female dogs were divided into four experimental groups of 10 animals each, treated orally for 20 days with 10mg/kg/day (G1) and 50mg/kg/day (G2) of pyridoxine hydrochloride (vitamin B6), 5μg/kg/day of cabergoline (G3), and with a placebo, in the case of the control group (G4). The effects of the treatments on milk production were investigated, as well as possible systemic side effects, macroscopic uterine and ovarian alterations, and uterine histology. During the investigated period, G2 and G3 were equally efficient (P>0.05) in lactation suppression, differing (P>0.05) from the other groups. There were no systemic side effects or uterine changes associated with administration of the studied drug. Vitamin B6 (50mg/kg) has shown to be a safe and economically viable alternative for lactation interruption in female dogs with pseudopregnancy.     

Genital tract pressures in mares II. Changes induced by oxytocin and prostaglandin F(2)alpha

The effects of oxytocin, prostaglandin F(2)alpha and a prostaglandin F(2)alpha analogue on uterine and vaginal pressures in the mare were measured using electronic catheter-tipped pressure transducers. Catheterisation for 70 minutes produced no significant change with time. Oxytocin caused a rapid rise in intrauterine pressure which had subsided 20 minutes later. Cloprostenol (prostaglandin F(2)alpha analogue) caused an increase in uterine pressure which started ten minutes after administration and lasted for the duration of the recording (60 minutes post-injection). Prostaglandin F(2)alpha produced a uterine pressure increase ten minutes after administration which declined over the next 40 minutes. The activity of the three drugs was not consistently affected by reproductive status (oestrus, dioestrus or anoestrus). There were no significant drug effects on intravaginal pressure.     

Changes in CD38 expression and ADP-ribosyl cyclase activity in rat myometrium during pregnancy: influence of sex steroid hormones

Cyclic ADP-ribose (cADPR), synthesized by CD38, regulates intracellular calcium in uterine smooth muscle. CD38 is a transmembrane protein that has both ADP-ribosyl cyclase and cADPR hydrolase enzyme activities involved in cADPR metabolism. CD38 expression and its enzyme activities in uterine smooth muscle are regulated by estrogen. In the present study, we examined CD38 expression, its enzyme activities, and cADPR levels in myometrium obtained from rats at 14-17 days of gestation (preterm) and at parturition (term). CD38 expression, ADP-ribosyl cyclase activity, and cADPR levels were higher in uterine tissues obtained from term rats compared with that of preterm rats, while activity of cADPR hydrolase did not significantly change. In an effort to address whether changes in estrogen: progesterone ratio that occur during pregnancy account for the observed effects on CD38 expression and function, we determined the effect of different doses of progesterone in the presence of estrogen on CD38 expression and its enzyme activities in uterine smooth muscle obtained from ovariectomized rats. In myometrium obtained from ovariectomized rats, estrogen administration caused increased CD38 protein expression and ADP-ribosyl cyclase activity. The estrogen-induced increases in CD38 expression and ADP-ribosyl cyclase activity were inhibited by simultaneous administration of 10 or 20 mg of progesterone. These results indicate that the estrogen:progesterone ratio determines CD38 expression and ADP-ribosyl cyclase activity. These changes in CD38/cADPR pathway may contribute to increased uterine motility and onset of labor.     

Suncus murinus: a new experimental model in emesis research

Effects of various emetic and antiemetic drugs were studied using Suncus murinus for its potential use as an experimental model in emetic research. Subcutaneous injection of nicotine bitartrate (10-15 mg/kg), veratrine sulfate (0.5-1.0 mg/kg), emetine dihydrochloride (40-80 mg/kg) and oral administration of copper sulfate (20-100 mg/kg) caused dose-dependent emesis in suncus. The ED50 of nicotine, veratrine, emetine and copper sulfate were 7.9, 0.4, 47.6 and 21.4 mg/kg, respectively. However, subcutaneously injected apomorphine hydrochloride (0.1-100 mg/kg), digitoxin (0.5-1.0 mg/kg) and orally administered emetine dihydrochloride (10-80 mg/kg) did not induce the vomiting. Chlorpromazine and promethazine decreased the emetic effect of nicotine, veratrine and copper sulfate, but scopolamine hydrobromide was not effective. These results indicate that the Suncus murinus is sensitive to various emetic and antiemetic drugs and can be used as a new experimental animal model for the emesis. Emetic behavior of suncus was discussed in comparison with other animals.     

Spontaneous and oxytocin-induced uterine motility in cyclic and postpartum mares

Intrauterine pressure was measured in three cyclic and two postpartum mares. Pressure was recorded using a catheter tip pressure transducer. The transducer was passed transcervically into the uterus.. In cyclic mares recordings were started on Day 1 of estrus and continued daily until ovulation as well as on Days 1 and 8 of diestrus. In postpartum mares recordings were started within 48 h after foaling and continued until the mares ovulated. The intrauterine pressure changes in postpartum mares was also recorded on Days 1 and 8 of diestrus. Spontaneous uterine contractions were recorded in cyclic mares for 30 min and in postpartum mares for 10 min. Induced uterine motilities were recorded for 30 min in both groups after the administration of oxytocin (40 USP, i.v.). Total area under the contraction curve in a 10-min period was used as a uterine motility quantitating unit. All mares demonstrated uterine contractions during estrus and diestrus. All mares demonstrated significant responses to oxytocin during estrus and diestrus. It appears that estrogen priming is not necessary for a significant uterine response to oxytocin.     

Amikacin sulfate in the cat: serum, urine and uterine tissue concentrations

Puerperal metritis and pyometra in non-breeding cats is frequently caused by gram-negative bacteria that are resistant to a variety of antibiotics. Amikacin has been found to be effective against pathogens associated with uterine infections in the mare and the woman, but its efficacy has not been studied in the cat. Serum concentrations of amikacin were determined in healthy adult cats (six male and six female) after administration of 5, 10, and 20 mg/kg body weight of amikacin sulfate, each dose given subcutaneously (s.c.), intramuscularly (i.m.) and intravenously (i.v.) to each of the cats using a repeat treatment design. In a subsequent experiment, the six females were given 10 mg/kg s.c. amikacin and samples of blood, urine and full-thickness uterine wall were taken at 40 and 120 minutes after treatment. Mean serum concentrations of amikacin peaked between 30 and 45 minutes after i.m. injection and between 45 and 60 minutes after s.c. injections. The serum amikacin concentration curves were similar regardless of dose or administration route except for a slightly longer retention time after the 20 mg/kg dose given i.m. and s.c. After s.c. injection of 10 mg/kg, the mean uterine concentration of amikacin at two hours after treatment was 4.1 ug/g; the concurrent mean serum concentration was 18.6 ug/ml.     

Effects of oral administration of tamoxifen, toremifene, dehydroepiandrosterone, and vorozole on uterine histomorphology in the rat

Tamoxifen, toremifene, DHEA, and vorozole inhibit tumor growth in rodent mammary carcinoma models and are promising chemotherapeutic agents for use against breast cancer development. In the present study, the effect of these agents on uterine histomorphology following oral administration to mature ovary-intact rats (n = 380) was examined. Animals received diet only (control), tamoxifen (0.4 and 1 mg/kg of diet; 10 mg/kg BW by daily gavage), toremifene (3-30 mg/kg of diet), DHEA (24-2000 mg/kg of diet), or vorozole (0.08-1.25 mg/kg BW by daily gavage) for 28 days and were either sacrificed or returned to a basal diet and then sacrificed 21 days later. Treatment with toremifene (all doses) or tamoxifen (1 and 10 mg/kg) for 28 days produced a decrease (P<0.05) in overall uterine size and myometrial thickness; however, uterine luminal and glandular epithelia cell height increased (P<0.05) compared with control. These compartmentalized uterotrophic and antiestrogenic effects of toremifene and tamoxifen were still apparent after 21 days post-treatment. Administration of DHEA (2000 mg/kg of diet) for 28 days had dramatic uterotrophic effects, increasing (P<0.05) overall uterine size and stimulating all three uterine compartments (epithelia, stroma, and myometrium). The other doses of DHEA, however, were not uterotrophic. Interestingly, after removal of DHEA from the diet, uterine weight and myometrial thickness decreased (P<0.05). Vorozole (1.25 mg/kg) administration for 28 days had differential, compartmentalized uterine effects, producing an increase (P<0.05) in epithelial cell height, a decrease (P<0.05) in stromal size, but no change in myometrial thickness. After 21 days postadministration of vorozole, luminal epithelial cell height was increased (P<0.05) compared with control. The data suggest that oral administration of tamoxifen, toremifene, DHEA, and vorozole results in differential, compartmentalized effects in the uterus that are highly dependent on treatment dose. The data may have implications for risk assessment of these agents prior to administration to healthy, cancer-free women.     

Effets immédiats du dimenhydrinate sur la contraction utérine e le rythme cardiaque foetal durant le travail.

The effects of intravenous administration of 100 mg of dimenhydrinate (Gravol) were studied in 20 patients during active spontaneous labour. The uterine activity and the fetal heart rate were monitored by an invasive technique. After administration of the medication the uterine activity increases significantly, and in 20% of the cases decelerations in the fetal heart rate of the hypoxic type occurred. Because of its unpredictable effects, this drug should be used with care during labour.     

The effect of locally administered PGE2 on the contractility of the nonpregnant human uterus in vivo.

The effect of locally administered prostaglandin E2 on the sensitivity and reactivity of the nonpregnant human uterus during the menstrual cycle was studied in seven women. An increase in uterine contractility in response to as little as 0.25 mug PGE2 could be observed during both the mid-proliferative and mid-secretory phases of the menstrual cycle, but around ovulation a marked decrease in sensitivity to PGE2 was noted. An inhibition of uterine motility was observed during menstruation in response to 30--40 mug PGE2. Endogenous E prostaglandin normally occurs in the secretory endometrium in levels comparable to the amount of exogenous PGE2 which elicited increased or decreased uterine activity in this study. These findings suggest that PGE2 may play an important role in the cyclical regulation of uterine motility during the menstrual cycle.     

Design and synthesis of a highly selective EP2-receptor agonist.

EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.     

Influence of environmental disturbances on uterine motility during pregnancy and parturition in rabbit and sheep

The effect of stressful stimuli on uterine motility during pregnancy and parturition was studied in sheep and rabbits. The effects of epinephrine and various alpha- and beta- adrenergic blocking agents were also investigated. By comparing the results of these experiments, the authors conclude that the increase in epinephrine level (stress response of the organism) is the direct cause of the observed changes in uterine motility.Both stress and epinephrine caused either an activation or an inhibition of uterine motility. The direction of the effect depended on the ratio of sex-steroid concentrations in the plasma. Blood plasma levels of oestradiol-17β and of progesterone were determined in the sheep. Both stress and epinephrine inhibited uterine motility only when plasma levels of oestradiol-17β were very high (oestrogen-domination). The biological relevance and clinical implications are discussed.