Indomethacin reduces contraction of isolated non-pregnant human uterine artery induced by prostaglandin F2 alpha

The purpose of this study was to explore whether cyclooxygenase products derived from endothelium or vascular smooth muscle participate in the response of human uterine artery to prostaglandin F2 alpha. Experiments were performed using human uterine arterial rings. Prostaglandin F2 alpha (0.4 nM-1 microM) induced contraction of human uterine arteries with both intact and denuded endothelium with similar potency and efficacy (pD2 values: 7.93 +/- 0.01 and 8.07 +/- 0.03 for vessels with and without endothelium respectively; maximal response values: 89.1 +/- 4.7% and 92.3 +/- 3.8% for vessels with and without endothelium respectively). Indomethacin (10 microM) significantly suppressed the maximum effects of prostaglandin F2 alpha and induced a shift towards the right of the prostaglandin F2 alpha concentration-response curves, regardless of the endothelial condition. On the other hand, in both types of preparations, OKY-046 (10 microM), an inhibitor of thromboxane synthesis, did not affect prostaglandin F2 alpha-induced contraction of human uterine arteries. It is concluded that in human uterine artery prostaglandin F2 alpha-induced contraction is mediated, at least in part, through constrictor prostanoid(s) of vascular smooth muscle origin that is not thromboxane A2.     

Effect of the vascular endothelium on norepinephrine-induced contractions in uterine radial arteries from the nonpregnant and pregnant human uterus

OBJECTIVE: Our purpose was to investigate the role of the endothelium in the human uterine arterial response to norepinephrine in the nonpregnant and pregnant states. STUDY DESIGN: Tissue was obtained from six pregnant and six nonpregnant women undergoing cesarean section or hysterectomy. Uterine radial arteries were isolated and subjected to norepinephrine dose-response curves with and without intact endothelium. RESULTS: Responses were obtained over a dose range of 10(-8) to 10(-4) norepinephrine. Initially there was no difference between vessels from pregnant and nonpregnant patients, but removal of the endothelium significantly increased the response in vessels from pregnant women. Addition of nitro-L-arginine methyl ester when the endothelium was intact did not alter the dose-response curves. CONCLUSIONS: In pregnancy human uterine radial arteries are more sensitive to norepinephrine than during the nonpregnant state. This increase is countered by an endothelium-derived relaxing factor. The factor is unlikely to be nitric oxide.     

A comparative study of uterine activity in labour induced with prostaglandin F2alpha or oxytocin and in spontaneous labour. I. Pattern of the uterine contractions

The uterine contraction patterns and the changes in fetal heart rate (FHR) were studied in cardiotocographic recordings from 26 women in oxytocin-induced labour, 26 women in PGF2alpha-induced labour and 24 women during the later part of spontaneous labour. The contraction patterns and their effect on the FHR did not differ between the three groups. During the course of labour an increasing steepness of the upward slope of the contraction wave with increasing intensity of the contraction was found. High frequency of atypical contraction patterns, suggesting some degree of uterine incoordination was found during the active phase of labour in 10 patients, 8 of whom were primiparae. This incoordination could not be related to the effect of induction with either drug. Incoordinated contractions were associated with longer duration of labour and a tendency to more pronounced acidosis in the infant at birth, although mean values still fell in the normal range. Ominous FHR patterns were only seen in 2 cases of uterine hyperactivity during induction of labour.     

Immediate X-radiation induced contractions of the isolated guinea pig terminal ileum: the localization of the effect by drugs

Tone and motility of the isolated guinea pig ileum were increased by irradiation with a dose of 10 krd. The maximal effect corresponds to that induced by 0.001 microng/ml acetylcholine or 0.3 microng/ml nicotine. The pharmacological analysis of this effect performed with acetylcholine and nicotine and several blocking agents including hexamethonium, atropine, tetrodotoxin, diphenhydramine, and verapamil suggests that radiation acts on the postganglionic parasympathetic neuron and the neuromuscular synapse. The mechanism of radiation is likely to consist of both an increased release of acetylcholine from the postganglionic neuron and a sensibilization of the cholinergic receptor site at the smooth muscle cell. The latter effect is thought to result from an increased contractile action induced by acetylcholine or nicotine in the irradiated ileal smooth muscle.     

Effect of calcium channel blockers and salbutamol on oxytocin and PGF2 alpha induced uterine contractions in rats

Calcium channel blockers verapamil (2, 10nM), diltiazem (11, 22nM), nifedipine (2.9, 14nM) and salbutamol (21, 42nM) produced concentration dependent inhibition of oxytocin induced contractions in non-pregnant rats. With verapamil and nifedipine the effect was more marked at both low and high doses. Verapamil (1,2nM), diltiazem (2.2, 11nM), nifedipine (1.4, 2.9nM) and salbutamol (2.1, 4.2nM) produced significant inhibitory effect on PGF2 alpha (0.3 microgram) induced phasic tension. However, basal tension was significantly reduced by salbutamol and nifedipine only.     

Alteration of vascular endothelium and endothelium smooth muscle interaction after carbogen gas perfusion of isolated rat and guinea pig heart

The aim of the study was to alter the vascular endothelium of the mammalian myocardium with respect to coronary flow regulation and vascular permeability. For this purpose, carbogen gas perfusion (GP) of Langendorff-type isolated rat and guinea pig heart was chosen. Perfusion of the hearts with carbogen gas was possible, as well as replacement of the GP by fluid perfusion. The energetic and mechanical state, the creatine kinase release, and the electron microscopic examination of the rat heart indicated only a moderate to minimal alteration of the cardiomyocytes after GP. As a result of GP a massive alteration of the vascular endothelium could be demonstrated in the rat heart, based on the release of the cytosolic endothelial marker enzyme, purine nucleoside phosphorylase, the partly altered vascular permeability and the morphologically detected endothelial damage to arterioles, capillaries and venules. Moreover, the reduced coronary flow response to short periods of anoxia (rat, guinea pig) and the inverted flow response to serotonin administration with maintained response to sodium nitroprusside (rat) in the post-gas perfusion period reflected an alteration of endothelial smooth muscular interaction in the rat and guinea pig heart. Furthermore, the distensibility of the coronary vasculature was increased in the rat and guinea pig heart in the post-gas perfusion period, where a relative autoregulatory behavior was maintained (rat) or partly maintained (guinea pig) in passively predilated vessels. In conclusion, carbogen gas perfusion of isolated hearts allows to induce preferred alteration of endothelium and endothelium-smooth muscle interaction.     

The course of induced labor after use of intracervical extra-amniotic prostaglandin F2 alpha in pregnant patients with EPH gestosis

The aim of our study was to assess the efficacy of labor induction among patients affected by EPH gestosis after intracervical extra-amniotic insertion of 15 mg PGF2 alpha in methyl-cellulose gel. We concluded that PGF2 alpha when given intracervically in methyl-cellulose gel is a highly effective inducer of cervical ripening process as well as subsequent uterine contractions, too. It should be stressed that in no case did we find blood pressure increase after such therapy.     

Effect of prostaglandin F2alpha on the lysosomal membranes of eye tissues

It was demonstrated that both in vitro and in intravenous injection of prostaglandin F2alpha there occurred labilization of the membranes of sclera and ciliary body lysosomes, in difference from the cornea in rabbits. Glycosidase activity appeared in the vitreous body under the effect of prostaglandin, which was absent under normal conditions.     

Altering conception of dairy cattle by gonadotropin-releasing hormone preceding luteolysis induced by prostaglandin F2 alpha

The objective of these experiments was to determine the effect on fertility of GnRH when used in conjunction with one or two injections of PGF2alpha. In Experiment 1, GnRH was administered 7 d before the second of two injections of PGF2alpha (14 d apart). The control group received two injections of PGF2alpha without GnRH. Conception was reduced from 63.5% for 74 controls to 48.7% for the 79 heifers and cows that had been treated with GnRH, but estrus detection and pregnancy rates were similar. In Experiment 2, 85 heifers and cows received GnRH at a random stage of the estrous cycle, followed in 7 d by PGF2alpha. Thirty to 32 h after PGF2alpha, a second dose of GnRH was given to induce ovulation of the preovulatory follicle, followed by one fixed-time insemination 18 to 19 h later (treatment designated as GnRH, PGF2alpha, and GnRH). Controls (n = 85) were given PGF2alpha and inseminated at estrus. Although conception rate was not different, one fixed-time insemination after the GnRH, PGF2alpha, and GnRH treatment tended (35.3%) to reduce fertility compared with effects of the control (47.1%). It is unclear how an injection of GnRH during the intervening week between two injections of PGF2alpha reduced fertility in Experiment 1. However, in Experiment 2, when GnRH was given 7 d before one injection of PGF2alpha and when ovulation was induced with a second GnRH injection, one fixed-time insemination seemed to produce acceptable fertility in dairy cows but probably less than that when inseminations were based on detected estrus.     

Synergistic effects of prostaglandin F2alpha and tumor necrosis factor to induce luteolysis in the pig

Telomerase activity was detected in germ cells, stem cells and cancer cells. In tumors of the ovary, an organ that contains germ cells, the authors examined availability to detect telomerase activity. Telomerase activity of malignant tumors was extremely high compared with that of normal ovaries and benign tumors. Strength and frequency of telomerase activity in malignant tumors was significant different from that in benign tumors. Telomere length tended to be smaller for malignant tumors of advanced stage, but no significant relationship between telomere length and telomerase activity and tumor stage could be recognized. Telomerase activity may be a useful marker for the diagnosis of ovarian tumors.     

Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe

OBJECTIVE: To determine whether water exposure causes middle ear contamination in patients with collar button tympanostomy tubes (TTs). METHOD AND DESIGN: An in vitro model of a human head that contained an auricle, external auditory canal, tympanic membrane with TT, middle ear, eustachian tube, and mastoid cavity was developed. Two electrodes connected to an external ohmmeter resided in the middle ear to detect water entry. The model was tested with 4 types of water exposure: showering, bathing, hair rinsing, and swimming. Statistical analysis was performed by the Fisher exact test. MAIN OUTCOME MEASURES: A positive test result corresponded to water entering the middle ear via the TT, confirmed by a resistance reading of zero on the ohmmeter. A negative test result indicated no change in the initial high resistance reading. RESULTS: No positive test results were obtained for showering (0 of 60 tests), hair rinsing (0 of 60 tests), or head submersion (12.7 cm) in clean tap water (0 of 60 tests). Ten positive test results were obtained for head submersion in soapy water (10 of 97 tests), which was statistically different from clean water (P< or =.007). Swimming pool depths of 30, 45, 60, and 75 cm elicited positive test results in 2 of 16, 3 of 18, 2 of 20, and 11 of 20 tests, respectively. A higher incidence of water entry into the middle ear occurred at depths of more than 60 cm (P< or =.001). No statistical difference between depths of 60 cm or less occurred (P= .88). CONCLUSIONS: Showering, hair rinsing, and head submersion in clean tap water do not promote water entry into the middle ear. Submersion in soapy water increases the probability of water contamination. Pool water infrequently enters the middle ear with head submersion, but the incidence increases with deeper swimming (>60 cm). These data provide further evidence that many water precautions frequently advised in patients with TTs are unnecessary.     

Preoperative cervical dilatation by small doses of prostaglandin F 2 alpha

To clarify the role of Ca ion in the rising phase of the sinoatrial (S-A) node action potential, the sigmoidal relationship between the maximum rate of rise of the action potential and the maximum diastolic potential was examined at various concentrations of Ca. The membrane potential was changed by applying a current across a single sucrose gap. The sigmoidal curve shifted toward the positive potential without a change in maximum value when the Ca concentration was increased from nominal "zero" to 10 mM. Therefore, it is concluded that Ca ion modifies the inactivation process of Na current which is responsible for the rapid rising phase of the S-A node action potential. The duration of the action potential and the maximum diastolic potential were decreased with an increase in Ca concentration. The observation that the overshoot of the action potential increased by 12 mV for a tenfold increase in concentration of Ca (within the range of 0.1-5.0 mM) suggests that the inward current of Ca ion may be responsible for the overshoot of the S-A node action potential.     

Effect of prostaglandin F2 alpha (PGF2 alpha) on oviductal nitric oxide synthase (NOS) activity: possible role of endogenous NO on PGF2 alpha-induced contractions in rat oviduct

The objective was to analyse differences in the epidemiological pattern of sudden death in infancy during two time periods--the Sudden Infant Death Syndrome (SIDS) 'epidemic': 1984-1989, and the period of rapid decline in the SIDS rate 1990-1996. Sex distribution, age, sleeping position, signs of infection, day of the week and place of death were registered and compared for the two time periods studied in all SIDS cases autopsied at the Institute of Forensic Medicine, Oslo. There were significantly more deaths in the age group under four months in the period 1984-89 than in the second period. Prone sleeping position, signs of infection, death outdoors and during the winter were more frequent during the first period than in the second. These features also were more frequent in the age group under four months than in the older babies during the first period. The shift in the epidemiological pattern after 1990, when the risk factor campaign was launched, indicates that prone sleeping position, cold climate, sleeping outdoors and infections seem to be risk factors that are particularly harmful to the youngest infants.     

Stimulation by prostaglandin F2alpha of acidic glycosaminoglycan production in cultured fibroblasts

The effect of PGF2alpha on the synthesis of hexosamine-containing substances (acidic glycosaminoglycans and glycoproteins) was studied in cultured fibroblasts derived from a rat carrageenin granuloma. Treatment with PGF2alpha ranging from 0.01 mug/ml to 20 mug/ml resulted in a significant increase of the production of these macromolecules by the cells. The stimulatory effect was found significant even at the low concentration of 10 ng/ml, and could be seen as early as 3h after exposure to PGF2alpha. The hexosamine-containing substances increased by PGF2alpha revealed that 80% of the increase was due to acidic glycosaminoglycans and the rest was due to glycoproteins.     

Biosynthesis of prostaglandin F2alpha from arachidonic acid and prostaglandin endoperoxides in the uterus

Formation of prostaglandin F2Alpha in the cow and guinea pig uterus microsomes was studied using 14C-labeled arachidonic acid and prostaglandin H2. The total conversion of arachidonic acid was of a low order and underwent fluctuations during the estrous cycle of the guinea pig, being highest towards the end of the cycle. Injections of beta-estradiol-3-benzoate also resulted in higher activity of the uterine prostaglandin synthetase. The uterine prostaglandin synthesizing system appeared to differ in several respects from that present in seminal vesicles, with regard to the proportions of the products formed and the effects of various agents, e.g. reduced glutathione. An inhibiting factor which supressed the fatty acid cyclo-oxygenase was found to be present in uterine preparations. Prostaglandin endoperoxide (prostaglandin H2) was very efficiently reduced to prostaglandin F2alpha by cow and guinea-pig uterus microsomes. Prostaglandin G2 also gave rise to prostaglandin F2alpha. Prostaglandin E2, on the other hand, was not reduced. Both the inhibiting factor and the endoperoxide reducing activity are likely to be parts of a highly specialized mechanism that modulates prostaglandin F2alpha formation in the uterus.     

Suppression of evoked IPSPs by arachidonic acid and prostaglandin F2 alpha

Arachidonic acid (AA) and certain prostaglandins appear to antagonize GABAA receptors in synaptoneurosomes [18]. We report here that perfusing hippocampal slices with AA or prostaglandin F2 alpha diminishes evoked IPSP conductance and increases CA1 pyramidal cell input resistance. The effects of the two compounds were similar, though not identical, in time course, magnitude, and response to washout. These findings suggest that high levels of AA and its metabolites may bias neurons towards excitation.