The effects of prostaglandin F2alpha on sperm output in boars

The effect of prostaglandin F2alpha (PGF2alpha) on the sperm output of six boars was investigated in two studies. Although PGF2alpha did not significantly affect sperm numbers in the ejaculate, a significantly longer (P less than 0.05) ejaculation of the sperm rich fraction occurred following injection of PGF2alpha. In the second study it was found that PGF2alpha produced a 49% increase (P less than 0.05) in the number of sperm in the sperm rich fraction of the ejaculate. The implications of these results on artificial breeding are discussed.     

Ocular penetration and bioconversion of prostaglandin F2alpha prodrugs in rabbit cornea and conjunctiva

The objective of this study was to identify prostaglandin F2alpha (PGF2alpha) prodrugs that have an optimal ocular absorption profile and therefore could be potentially useful for the treatment of glaucoma. Rabbit cornea, conjunctiva, and iris/ciliary body were mounted in a flow-through chamber to evaluate the permeability and bioconversion of PGF2alpha and its prodrugs. The prodrugs tested were PGF2alpha 1-isopropyl, 1,11-lactone, 15-acetyl, 15-pivaloyl, 15-valeryl, and 11,15-dipivaloyl esters. After 4 h in the donor or acceptor compartments, the products and formation of PGF2alpha were analyzed by HPLC. Effects on intraocular pressure and ocular surface hyperemia were also determined. All prodrugs penetrated the rabbit cornea faster than PGF2alpha by 4- to 83-fold. All prodrugs penetrated conjunctiva faster than PGF2alpha, except the 15-acetyl ester prodrug, which was equally permeable. No direct correlation between drug lipophilicity and permeability across the cornea or conjunctiva was apparent. The most metabolically stable prodrug was the 1,11-lactone, followed by the 11,15-dipivaloyl, 15-pivaloyl, 15-acetyl, 1-isopropyl, and the 15-valeryl esters, the latter of which was extensively converted to PGF2alpha. A separation index for various prodrugs was calculated from the ratio of the bioavailable PGF2alpha for ocular hypotension to the bioavailable PGF2alpha for hyperemia. The highest separation index was observed for the 1,11-lactone prodrug (2.33), followed by the 11,15-dipivaloyl ester prodrug (1.80). Thus the 1,11-lactone and 11,15-dipivaloyl ester prodrugs appeared to be superior to the others in providing bioavailable PGF2alpha for ocular hypotension, while minimizing hyperemia. The favorable separation index for these compounds appeared to be due to their metabolic stability at the corneal surface and conjunctiva combined with sufficient bioavailability for ocular hypotension.     

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.     

Radioimmunoassay for urinary metabolites of prostaglandin F2alpha

Antibodies against the main urinary metabolite of PGF2alpha in the human, 5alpha, 7alpha-dihydroxy-11-ketotetranorprosta-1,16-dioic acid, were raised in rabbits. The compound was coupled selectively in the omega position to bovine serum albumin prior to injection. The resuling antibodies did not distinguish between tetranor compounds varying only in structure at the omega carbon, and thus the assay could be used also for other metabolites of PGF2alpha, e.g. the main urinary metabolite in the guinea pig, 5alpha,7alpha-dihydroxy-11-ketotretranorporstanoic acid. Labeled ligands for the assays were prepared either in vivo by injection of [17, 18-3H]-PGF2alpha into humans after several days treatment with indomethacin, or in vitro by incubation of [17, 18-3H]-15-keto-13, 14-dihydro-PGF2alpha with mitochondria from rat liver. The sensitivity of the assay was 10 pg or 4 pg with these two preparations, respectively. The assay was employed for a number of measurements: normal daily excretion in a number of humans; excretion of urinary metabolites during treatment with prostaglandin synthetase inhibitors in human subjects, or after intravenous injection of PGF2alpha; excretion during human pregnancy; and prostaglandin production in the guinea pig during normal estrous cycles and pregnancies and after estrogen treatment. The results of these studies were in several cases compared to similar measurements earlier performed using mass spectrometric methods, and were found to agree well. Thus, this radioimmunoassay provides a simple and accurate method for estimating prostaglandin production, particularly suitable for long-term studies and for cases where repeated blood sampling must be avoided.     

Dexamethasone inhibits the pyrogenic activity of prostaglandin F2 alpha, but not prostaglandin E2

The effect of dexamethasone on prostaglandin (PG) E2- and PGF2 alpha-induced fever was studied in rats. Intracerebroventricular injection of PGE2 and PGF2 alpha (500 ng) induced increases in body temperature (maximal temperature rises of 0.97 +/- 0.13 degrees C and 0.78 +/- 0.18 degrees C, respectively, vs. vehicle 0.12 +/- 0.09 degrees C) of unrestrained rats maintained within the thermoneutral zone. PGE2-induced fever peaked earlier and the defervescence was faster when compared to the response induced by PGF2 alpha. Subcutaneous pre-administration of dexamethasone (0.5 mg/kg) did not affect PGE2-induced fever (maximal temperature rise of 1.00 +/- 0.08 degrees C), but completely prevented the pyrogenic activity of PGF2 alpha (maximal temperature rise of 0.16 +/- 0.16 degrees C). Neither PGE2- nor PGF2 alpha-induced fever was significantly altered (maximal temperature rises of 0.90 +/- 0.11 degrees C and 0.64 +/- 0.14 degrees C, respectively) by intraperitoneal administration of indomethacin (2 mg/kg). These results demonstrate for the first time that glucocorticoids, in addition to inhibiting endotoxin- and cytokine-induced fever, can also modulate the pyrogenic activity of some prostaglandins, possibly via suppression of the synthesis of corticotropin-releasing factor, indicating that multiple mechanisms may be involved in the antipyretic activity of these steroids.     

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.     

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.     

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.     

Effects of prostaglandin E2 and F2 alpha on the skeleton of osteopenic ovariectomized rats

This article contains the histomorphometric evaluation of the effects of prostaglandin F2 alpha (PGF2 alpha) on cancellous bone from the lumbar vertebra and cortical bone from the tibial shaft of ovariectomized, osteopenic rats. These effects were then compared with those of prostaglandin E2 (PGE2). Three-month-old rats were either ovariectomized (ovx) or sham-ovx. Then, either PGF2 alpha or PGE2 in doses of 1 and 3 mg/kg/day was given subcutaneously for 21 days at 150 days post ovx. Histomorphometric analysis was performed separately on both the primary and secondary spongiosae of the fourth lumbar vertebral bodies (LVB) and on tibial shafts. The ovx rats exhibited osteopenia in both primary (-23% to -37%) and secondary (-20%) spongiosae of the LVB, but not in the tibial shafts at 150 and 171 days post ovx. In the LVB, PGE2 in doses of 1 or 3 mg/kg/day for 21 days restored trabecular bone volume to the levels of sham-ovx controls in the primary spongiosa. However, in the secondary spongiosa, the treatments only thickened the trabeculae. The effects of the PGF2 alpha treatment were similar to those of the PGE2 in both the primary and the secondary spongiosae. While both PGF2 alpha and PGE2 treatments stimulated bone formation in the LVB as indicated by the increases in labeled perimeter, tissue and bone area-based bone formation rates, PGE2 is about 10 times more potent than PGF2 alpha in these effects. The PGE2 treatment also elevated activation frequency in the LVB, while the PGF2 alpha treatment did not. The treatments differed in that PGE2 at these dose levels did not alter the eroded surface in the LVB while PGF2 alpha decreased it significantly. Thus, the increase of the ratio of labeled to eroded perimeter in the LVB in PGF2 alpha-treated animals was much more than that in PGE2-treated animals. In the tibial shafts, PGE2 in doses of 1 and 3 mg/kg/day produced new marrow trabeculae in 2 of 6 and 3 of 6 of the ovx rats. However, no new trabecula was found in PGF2 alpha-treated tibial shafts. Higher doses of PGE2 also increased periosteal labeled perimeter, MAR, and BFR/BS, while PGF2 alpha did not produce any significant change in these parameters. Both PGE2 and PGF2 alpha in doses of 1 and 3 mg/kg/day increased the labeled perimeter, MAR and BFR/BS and decreased the eroded perimeter in the endocortical surface. We concluded that both PGF2 alpha and PGE2 in doses of 1 and 3 mg/kg/day for 21 days exhibited anabolic bone effects. The effects were mostly confined to an increase in trabecular volume in the primary spongiosa of the LVB and in the endocortical surface of tibial shafts. The tissue level mechanism behind this appears to be that PGE2 and PGF2 alpha can both stimulate osteoblast recruitment and activity. Overall, we found PGE2 to be more potent than PGF2 alpha at the same dose level at the endocortical surface. Furthermore, new marrow trabecular bone formed only after PGE2 treatment. PGF2 alpha differed from PGE2 by significantly reducing the trabecular eroded surface in ovx rats.     

Radioimmunoassay of main urinary metabolite of prostaglandin F2alpha

Radioimmunoassay of 5alpha, 7alpha-dihydroxy-11-keto-tetranorprosta-1,16-dioic acid, main urinary metabolite of prostaglandin F2alpha (PGF2alpha), was performed using an antiserum produced in the rabbit. The antibody in 100 mu1 of 1,600-fold diluted antiserum binds with 60 picograms of metabolite. The main urinary metabolite level fell when flufenamic acid, a prostaglandin synthetase inhibitor, was given to rats. In contrast, it was significantly elevated when PGF2alpha was administered.     

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.     

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.     

Changes in refractoriness of rabbit corpora lutea to a prostaglandin F2 alpha analogue, alfaprostol, during pseudopregnancy

Seventeen care providers were interviewed about their caring experiences on a hospital psychiatric ward. The interviews focused on the meaning of their work, including the care they provide and the nature of the patient as a person. The study was guided by a phenomenological hermeneutic perspective inspired by Ricoeur (1976). The analysis focused on context and form. Three themes illuminate the meaning of care provided. These themes are as follows; being in the midst of human storage, moving towards a human care of relations, and struggling with 'the old' and 'the new'. Experiencing work as being in the midst of a human storage reflects the historical and human situation of warehousing psychiatric patients. The care providers are experiencing a shift in their view of the patient and the meaning of their work, towards a more human care of relations. For these care providers, there is a struggle between the past, the present and the future. This struggle between 'the old' and 'the new' conveys a struggle between doing as a nurse, which dominates the past, and relating, which is, or needs to be, the current and future focus in psychiatric care. The shift in view distinguished itself by the care providers viewing the patient as being vulnerable and having problems with relations. The results have been interpreted and discussed in the light of a previously published interview study with the patients, carried out at the same time on the same ward. Attending to ingrained attitudes of the past and their influence on new approaches to care is essential to understanding not only changes in ways of doing nursing tasks, but also ways of relating.     

The effects of transcorneal administration of prostaglandin E2 on rabbit eyes

The pharmacologic effects of prostaglandin E2 (PGE2) on the anterior ocular segment were investigated. PGE2 was administered with a glass cylinder attached to the cornea in concentrations ranging from 0.05 to 500 micrograms/ml. The intraocular inflammatory reaction was assessed according to the changes in the anterior chamber flare, ocular tension, and components of the aqueous humor. We also performed experiments designed to inhibit the reactions induced by PGE2 using anti-inflammatory agents. The PGE2 elicited a single peak reaction in the anterior chamber flare, which recovered after several hours, and a transient elevation in the ocular tension in the early stage after PGE2 administration. Quantitative analysis of these two reactions revealed that both were dependent on the dose of PGE2 administered. The concentrations of ascorbic acid and glutathione, particularly that of the reduced form of the latter, were transiently reduced in the aqueous humor. The anterior chamber flares were suppressed by agents that inhibit arachdonic acid metabolism. These findings suggest that the metabolism of arachdonic acid becomes newly activated as a result of stimulation by PGE2 of extrinsic origin.