Administration Of Prostaglandin E2 Research Articles

123. Corticosteroids, but not catecholamines, mediate stress- and surgery-induced suppression of plasma IL-12 levels in rats: A second-phase response of stress-induced immune perturbations

We recently reported that various stress paradigms suppress plasma IL-12 levels. The aim of this study was to elucidate potential neuroendocrine mediating mechanisms. Administration of prostaglandin-E2, epinephrine, and corticosterone, significantly reduced plasma IL-12 levels. However, when subjecting animals to stress or surgery, only the glucocorticoid-receptor blocker, mifepristone, and the COX-2 inhibitor, etodolac, but not α- or β-adrenergic blockers, attenuated the reduction of plasma IL-12 levels. As epinephrine administration did reduce IL-12 levels, we subjected adrenalectomized and sham-operated rats to epinephrine and/or corticosterone administration. While corticosterone reduced IL-12 levels in both conditions, epinephrine did so only in sham operated animals, indicating that its effects are mediated through elevated endogenous corticosterone levels, which we confirmed. In addition, blockade of prostaglandin production during surgery also reduced corticosterone levels, suggesting that at least some of the effects of prostaglandin are corticosterone-mediated. In accordance, but contrary to some reports, our in vitro studies indicated that corticosterone, but not prostaglandin-E2 or epinephrine, reduced spontaneous and induced IL-12 production levels. We thus hypothesize that stress-induced immune perturbations rely on two mechanisms: One mediated through activation of short-lasting processes by catecholamines and/or prostaglandins, and a second leading to long-lasting perturbations through glucocorticoids. IL-12 has a long half-life time and is prominent in inducing Th1 differentiation – a long lasting process that, as observed herein, is indeed suppressed through elevated corticosteroids, but not catecholamines.

Duktus Bağımlı Konjenital Kalp Hastalıklarında Oral Prostaglandin E1 Tedavisinin Değerlendirilmesi

Purpose: Intravenous prostaglandin E1 (PGE1) infusion is a treatment which has been proven to be effective in ductus dependent congenital heart disease. However, PGE1 is very expensive, needed continuous infusion and its supply is difficult by every center. When its long term use is necessary, these problems become more important. The aim of this study was to show whether oral PGE1could keep the ductus open or not till the supply of intravenous PGE1. Method: Ten patients, who were admitted to newborn intensive care unit with the diagnosis of ductus dependent congenital heart disease and received oral PGE1 till the supply of intravenous PGE1, were evaluated. The PO2 with the arterial blood gas analysis and SO2 levels with pulse oxymeter at skin were recorded before and after the administration of oral and intravenous PGE1. Results: The mean oral PGE1 initiation age was 5.5 hours (0.5-25), and mean administration period was 28 hours (18-46). It was observed that the PO2 and SO2 levels of patients measured 2 hours after the initiation of oral PGE1 were significantly increased compared to the levels before initiation of PGE1. The improvement in PO2 and SO2 levels continued till the initiation of intravenous PGE1. It was also observed that the PO2 and SO2 levels of patients measured 2 hours after the initiation of intravenous PGE1 were slightly increased compared to levels before initiation of intravenous PGE1. Conclusion: Although intravenous PGE1 is more effective than oral PGE1 in short term usage, oral PGE1 is also sufficiently effective in keeping the dustus open. For this reason until the intravenous PGE1 is supplied oral PGE1 may be used as an alternative treatment choice. We think that in long term use oral PGE1, which is cheaper and easy to use, could be used instead of intravenous PGE1 without need of admission to hospital and opening intravenous line. However for this further studies are needed to confirm this assumption.

Effect of intrathecal administration of E‐series prostaglandin 1 receptor antagonist in a cyclophosphamide‐induced cystitis rat model

To investigate the effect of intrathecal administration of E-series prostaglandin 1 antagonist in cyclophosphamide-induced murine cystitis. Female Wistar rats were used for this experimental study. Intrathecal administration of E-series prostaglandin 1 antagonist (ONO-8711; 0.5, 5 and 50 µg) in sham controls and rats with cystitis induced by a single intraperitoneal injection of cyclophosphamide (300 mg/kg) was assessed by evaluating micturition pressure and intercontraction interval using a conscious-filling cystometry at 48 h after cyclophosphamide or saline injection. In both groups, prostaglandin E2 concentrations and the expression of E-series prostaglandin 1 receptor in the spinal cord were measured by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Rats with cyclophosphamide-induced cystitis showed a shorter intercontraction interval compared with controls, where the cumulative intrathecal administration of ONO-8711 did not significantly change micturition pressure or intercontraction interval compared with the baseline. In rats with cyclophosphamide-induced cystitis, each dose of ONO-8711 significantly increased the intercontraction interval compared with the baseline (46% increase at 50 µg intrathecally). Polymerase chain reaction revealed the expression of E-series prostaglandin 1 receptor in the spinal cord of both sham and cyclophosphamide-induced cystitis rats. In rats with cyclophosphamide-induced cystitis, PGE2 concentration in the dorsal horn of the L5-6 spinal cord was significantly higher than that in controls (3.55 ± 1.24 vs 0.99 ± 0.06 pg/mg tissue). In rats with cyclophosphamide-induced cystitis, urinary frequency seems to be caused by prostaglandin E2 acting on E-series prostaglandin 1 receptor at the level of the spinal cord. Blockade of the spinal E-series prostaglandin 1 receptor by ONO-8711 might have a therapeutic potential in the control of interstitial cystitis/bladder pain syndrome.

Prostaglandin E1 facilitates inotropic effects of 5-HT4 serotonin receptors and β-adrenoceptors in failing human heart

Prostaglandins have displayed both beneficial and detrimental effects in clinical studies in patients with severe heart failure. Prostaglandins are known to increase cardiac output, but the mechanism is not clarified. Here, we tested the hypothesis that prostaglandins can increase contractility in human heart by amplifying cAMP-dependent inotropic responses. Contractility was measured ex vivo in isolated left ventricular strips and phosphodiesterase (PDE) and adenylyl cyclase (AC) activity was measured in homogenates or membranes from failing human left ventricles. PGE(1) (1µM) alone did not modify contractility, but given prior, amplified maximal serotonin (5-HT)-evoked (10µM) contractile responses mediated by 5-HT(4) receptors several fold (24±7% with PGE(1) vs. 3±2% above basal with 5-HT alone). The 5-HT(4)-mediated inotropic response was amplified by the PDE3 inhibitor cilostamide and further amplified in combination with PGE(1) (26±6 vs. 56±12% above basal). PGE(1) reduced the time to reach 90% of both the maximal 5-HT- and isoproterenol-evoked inotropic response compared to 5-HT or isoproterenol alone. PGE(1) did not modify PDE activity in the homogenate, either alone or when given simultaneously with PDE3 and/or PDE4 inhibitors. Neither 5-HT- nor isoproterenol-stimulated AC activity was significantly amplified by PGE(1). Sensitivity of ventricular strips to Ca(2+) was not enhanced in the presence of PGE(1). Our results show that PGE(1) can enhance cAMP-mediated responses in failing human left ventricle, through a mechanism independent of PDE inhibition, amplification of AC activity or increasing sensitivity to calcium. This effect of PGE(1) possibly contributes to the increase of cardiac output, independent of decreased afterload, observed after prostaglandin administration in humans.

Partusinductie bij de zeug

Partusinductie verhoogt het toezicht tijdens het werpen, waardoor het geboortegetal kan toenemen. Wanneer partusinductie echter niet correct wordt toegepast, kan dit leiden tot vroeggeboorte. Daarom mag partusinductie pas ten vroegste twee dagen vóór de gemiddelde drachtduur van de zeugen op een bedrijf worden uitgevoerd. Voor partusinductie bestaan verschillende protocols, zoals de eenmalige toediening van prostaglandinen, de dubbele toediening van prostaglandinen met zes uur interval (split-dose-techniek) en de combinatie van prostaglandinen met oxytocine 24 uur later en verschillende toedieningswegen, zoals intramusculaire injectie in de nekregio en injectie in de buurt van de vulva. Andere strategieën bestaan maar zijn minder effectief en/of worden minder frequent gebruikt. Na een eenmalige injectie van prostaglandinen werpt 60% van de zeugen binnen de werkuren (22-32 uur na injectie). Met de split-dose-techniek of de combinatie van prostaglandinen en oxytocine 24 uur later is dit 80%. Bij incorrect gebruik is oxytocine echter een risicofactor voor asfyxie bij biggen. Het wel of niet toepassen van partusinductie en welk protocol het beste wordt gebruikt hangen af van het bedrijf en de wensen van de veehouder.

Porcine uterus cryopreservation: An analysis of contractile function using different uterotonics

Cryopreservation of whole organs has become increasingly successful in recent years, and establishing reliable methods for confirming the success of specific cryopreservation procedures has therefore become extremely important. On the assumption that methods such as histological evaluation do not provide definitive evidence of long-term cryopreservation and that clear signs of conserved function in an organ are good evidence of its viability, contractile function was analysed in porcine uteri (n=60), either after long-term (group A) or short-term (group B) cryopreservation and post-thaw treatment with three different uterotonics. A slow freezing protocol was used to preserve the organs. Fifteen fresh uteri were analysed similarly for contractile function, which was evaluated by measuring intrauterine pressure after administration of oxytocin, prostaglandin E1 (PGE1), and carbachol. After cryopreservation, all but three uteri (95%) showed rhythmic contractions similar to those in fresh uteri except for differences in the heights of contraction peaks, with lower contractions in PGE1 subgroup B (P<0.05). With the exception of three nonresponsive uteri in group A, there were no differences in contractility between uteri after long-term cryopreservation and fresh uteri. The results of this study thus contribute to the debate on whether slow freezing or vitrification techniques are best for whole-organ cryopreservation. In summary, (1) preservation of muscular function in porcine uteri is feasible with a slow freezing protocol; (2) measurement of contractile function following administration of uterotonics is a useful method of confirming functionality; and (3) long-term cryopreservation does not significantly impair post-thaw contractibility in comparison with fresh uteri.

A new technique for the correction of hypoplastic left heart syndrome

Hypoplastic left heart syndrome (HLHS) inevitably results in death within a few weeks of birth, and the surgical treatment for this condition involves three complex surgeries that are associated with a high mortality and cost (1). The mortality rates for the first-stage procedure range from 25-80% at medical centers worldwide. Moreover, many children (possibly as many as 50%, according to hospitals where accurate records are kept) with this disease are not referred for surgery and progress to death within days or weeks (2-4). The two conventional techniques that are used for the Norwood procedure (the first-stage surgical correction) involve the construction of a systemic pulmonary shunt. This procedure performed using the Blalock-Taussig technique leads to a diastolic systemic pulmonary flow that mimics systemic valve insufficiency. When performed using the Sano modification technique, the Norwood procedure involves building a tube between the systemic ventricle and the pulmonary artery; this technique avoids the diastolic systemic pulmonary flow but allows the blood in the lungs to reflux to the single ventricle, which increases the volume overload. This overload associated with ventriculotomy may lead to dysfunction of the ventricle and arrhythmia. Moreover, both techniques necessitate the use of an artificial tube and carry a risk for thrombosis or stenosis (5-9). Additionally, fabrication of the neo-aorta is a laborious technique that requires the extended use of extracorporeal circulation (ECC). Hybrid approaches involving the maintenance of the patent ductus arteriosus with the implantation of a stent (10,11) or the prolonged administration of prostaglandin E1 (12) associated with the banding of the pulmonary branches simplifies the surgical approach but have yielded unsatisfactory results (13,14).

Pre-induction of labour: comparing dinoprostone vaginal insert to repeated prostaglandin administration: a systematic review and meta-analysis

Objective: To assess the efficacy and safety of the dinoprostone vaginal insert compared to repeated prostaglandin administration (including dinoprostone and misoprostol) in women at term. Methods: Electronic databases and additional handsearching were used to identify randomized controlled trial (RCT). We included studies reporting data separately for nulliparous and/or multiparous in women with unfavourable cervix (Bishop <5) and intact membranes. The primary efficacy outcome was caesarean section (CS) rate. Primary safety outcome was uterine hyperstimulation requiring immediate delivery. Results: Eighteen RCTs were eligible and seven studies were included (totally 911 patients). The dinoprostone vaginal insert reduces CS rate in nulliparous women of 24% compared to the other ways of administration (RR = 0.76, 95% CI = 0.59, 0.98). The risk of oxytocin use is reduced with the use of vaginal insert (RR = 0.64, 95% CI = 0.42, 0.99). The risk of hyperstimulation is statistically higher in nulliparous women using vaginal insert than the other ways of administration with RR = 2.17, 95% CI = 1.08,4.33. Conclusions: In nulliparous women with unprepared cervix and intact membranes vaginal insert perform better than repeated vaginal doses since it is associated with more vaginal deliveries and less oxytocin use. Although vaginal insert is associated with more uterine hyperstimulation, it shows a protective effect toward caesarean section.

Effects of prostaglandin administration 10 days apart on reproductive parameters of cyclic dairy nulliparous goats

This study reported the effects of prostaglandin (PGF2a) administration 10 days apart on reproductive parameters of cyclic artificial inseminated (AI) nulliparous Alpine (n=9) and Saanen (n=9) goats. Animals received two doses of 22.5mg PGF2a 10 days apart. After 1st and 2nd PGF2a administrations, estrus was monitored at 12 h intervals, with a buck teaser. Plasma progesterone concentration (ng/mL) was determined from blood sampled on day 0 (1st PGF2a) and the following 5, 10 (2nd PGF2a), 15, 20, 25 and 30 days. After the onset of the second estrus, females were transrectally (5 MHz probe) scanned at 4 hour intervals until at least 8h after ovulation. Pregnancy was checked through transrectal ultrasound on days 20, 25, 30, 35 and 90 after insemination. All parameters studied did not differ between breeds (P&gt;0.05). Estrous response and interval to estrus, respectively, after 1st (78.9% and 50.6±17.2h) and 2nd PGF2a (88.9% and 50.0±14.8h) administration did not differ (P&gt;0.05). Overall animals ovulating (100.0%), interval to ovulation after 2nd PGF2a (64.5±19.5h) and after estrous onset (18.0±9.1h), ovulation rate (1.3±0.5), diameter of ovulatory follicle (8.1±1.1mm) were recorded. Embryo loss occurred before day 30 of pregnancy. Estrus can be efficiently synchronized in nulliparous Alpine and Saanen goats with two doses of prostaglandin 10 days apart.

11-deoxy prostaglandin F2α, a thromboxane A2 receptor agonist, partially alleviates embryo crowding in Lpar3(−/−) females

To determine cyclooxygenase-derived prostanoid signaling in alleviating embryo crowding in the Lpar3((-/-)) females. Experimental mouse model. Research laboratories. Wild-type, Lpar3((+/-)), and Lpar3((-/-)) mice. Intraperitoneal (IP) administration of prostaglandin E(2) (PGE(2)), cPGI (a stable analogue of PGI(2)), and 11-deoxy prostaglandin F(2α) (11-deoxy PGF(2α), a thromboxane A(2) receptor agonist) to preimplantation gestation day 3.5 Lpar3((-/-)) females. Implantation sites were detected by blue dye reaction and embryo spacing was determined by the distribution of the implantation sites along the uterine horns on gestation day 4.5; pregnancy outcome was measured by litter size at birth. Administration of PGE(2) + cPGI on gestation day 3.5 Lpar3((-/-)) females restored on-time implantation but did not affect embryo spacing or the number of implantation sites detected on gestation day 4.5; PGE(2) + cPGI treatment increased litter size at birth. Administration of PGE(2) + cPGI + 11-deoxy PGF(2α) on gestation day 3.5 Lpar3((-/-)) females rescued on-time implantation, partially dispersed the clustered implantation sites normally observed in the Lpar3((-/-)) females, increased the number of implantation sites detected on gestation day 4.5, and increased litter size at birth. The thromboxane A(2) receptor agonist 11-deoxy PGF(2α) can partially alleviate embryo crowding in the Lpar3((-/-)) females and embryo crowding likely contributes to reduced litter size in the Lpar3((-/-)) females.

Protective Effect of Prostaglandin E&lt;sub&gt;1&lt;/sub&gt; on Radiation-Induced Proliferative Inhibition and Apoptosis in Keratinocytes and Healing of Radiation-Induced Skin Injury in Rats

We examined the effects of prostaglandin E₁ (PGE₁) on radiation-induced proliferation inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in a rat model. PGE₁ had a protective effect on radiation-induced growth inhibition in keratinocytes in vitro, but not in fibroblasts. Varying concentrations of PGE₁ were subcutaneously administered into the posterior neck region. X-irradiation at a dose of 20 Gy was administrated to the lower part of the back using a lead sheet with two holes 30 min to 1 h before or after the administration of PGE₁. Although X-irradiation induced epilation, minor erosions, or skin ulcers in almost all rats, PGE₁ administration prior to irradiation reduced these irradiation injuries. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling showed that proportions of apoptotic keratinocytes in the X-irradiated skin of PGE₁-administered rats were significantly lower than for those in the skin of rats which did not receive PGE₁. Cutaneous full-thickness defective wounds were then formed in X-irradiated areas to examine the time course of wound healing. Wound healing was significantly delayed because of X-irradiation, but PGE₁ administration prior to irradiation led to a significantly shorter delay in wound healing compared with controls. Decreasing delay in wound healing was correlated with concentration of PGE₁ administrated. Thus, PGE₁-administration may potentially alleviate the radiation-induced skin injury.

Differences in Apoptotic Status in the Bovine Placentome between Spontaneous and Induced Parturition

We conducted this study to analyze apoptotic changes in the bovine placentome at spontaneous and induced parturition. Cows delivered i) after the administration of dexamethasone followed by prostaglandin F(2α) and estriol, ii) after the administration of prostaglandin F(2α) and estriol or iii) spontaneously. Prepartum changes in plasma progesterone and estradiol-17β concentrations were similar between spontaneous and induced parturition. Messenger RNA of BCL2-related protein A1 (BCL2A1), an antiapoptotic gene, was expressed by trophoblast binucleate cells and caruncular epithelial cells. Quantitative RT-PCR showed that the expression of BCL2A1 mRNA in cotyledonary and caruncular portions was significantly lower in spontaneous parturition than induced parturition. The expression of BCL2-associated X protein (BAX) mRNA, a proapoptotic gene, was significantly higher in cotyledons at spontaneous parturition than parturition induced without dexamethasone. Caspase-3 (CASP3) mRNA and pre-activated CASP3 protein were predominantly detected in caruncular epithelial cells regardless of how parturition proceeded. Activated CASP3 protein was found in trophoblast uninucleate cells and binucleate cells rather than caruncular epithelial cells. In spontaneous parturition, intense staining of activated CASP3 was detected in caruncular epithelial cells. Spontaneous and dexamethasone-induced parturition increased apoptotic cells in the placentome compared with parturition induced without dexamethasone. The number of binucleate cells was significantly decreased in spontaneous parturition. The present results suggest that although the clinical dose of dexamethasone induces apoptosis in the placentome at term, neither dexamethasone nor prostaglandin F(2α) evoke normal physiological changes in the placentome during delivery such as a change in the balance of apoptosis-related genes and disappearance of binucleate cells.

Prostaglandins and its analogues : An approach for treatment of anoestrus and to enhance breeding efficiency

Cloprostenol is a synthetic prostaglandin F analogue. It is a FP (Prostaglandin F) receptor agonist, which shows 2· powerful luteolytic effects. It also stimulates the contraction of uterine and bronchial smooth muscle and produces vasoconstriction in some vessels. Anoestrous may be due to some conditions like abnormal pregnancy, early pregnancy, pyometra, endometritis, retention of placenta, maceration and mummification. So, get rid of this conditions cloprostenol is widely used. It has been now in vogue to administer PGF or its analogue in early 2· postpartum cows and buffaloes in order to hasten early resumption of cyclic ovarian activity and thereby to increase the reproductive efficiency. To improve reproductive efficiency, it is necessary to inseminate cows early in the breeding season so that, thereby achieving a more compact calving season. Breeding efficiency is increased by means of synchronization of estrus, conception rate and pregnancy rate. Estrus synchronization can be achieved by lysis of corpus luteum by administration of prostaglandin (PGF ) or its synthetic analogue on 5-17 2· days of the estrus cycle. The cows will return to estrus within 3-5 days. The effective therapeutic doses for cloprostenol are 500 µg in cattle and 175 µg in pigs. However, for R-cloprostenol, the recommended doses are: 150 µg in cattle and 75 µg in pigs. In both cases, it is administered by the intramuscular route.

Histopathologic investigation of the effects of prostaglandin E2 administered by different methods on tooth movement and bone metabolism

ObjectiveThe aim of this study was to investigate and compare the in vivo effects of prostaglandin E2 (PGE2) administered by different methods on orthodontic tooth movement and bone metabolism macroscopically, histopatologically, and biochemically.MethodsForty-five young adult New Zealand rabbits were randomly divided into 3 experimental groups (n = 10/group), 1 positive control group (n = 10), and 1 negative control group (n = 5). The experimental rabbits were fitted with springs exerting 20-g reciprocal force on the maxillary incisors and PGE2 (10 µg/mL) was administered by the intravenous, submucosal, or intraligamentous route after appliance insertion and on days 1, 3, 7, and 14 thereafter. All rabbits were sacrificed on day 21 and their premaxillae were resected for histologic evaluation.ResultsTooth movement was observed in the experimental and positive control groups, but the intraligamentous PGE2 group had the highest values of all analyzed parameters, including serum calcium and phosphorus levels and osteoclastic and osteoblastic populations (p < 0.001).ConclusionsSubmucosal and intraligamentous PGE2 administration significantly increases orthodontic tooth movement and bone metabolism, but the intraligamentous route seems to be more effective.

Medical methods for first trimester abortion

Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. To compare different medical methods for first trimester abortion. The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted. Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure. Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software. Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups. Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.

Prostaglandins for adult liver transplanted patients.

Prostaglandins may reduce ischaemic injury after liver transplantation. Several small randomised trials have evaluated the effects of prostaglandins in patients undergoing liver transplantation. Results of these trials are inconsistent, and none has enough power to reliably exclude effects of prostaglandins. To assess the benefits and harms of prostaglandin E1 or E2 in adult liver-transplanted patients. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS (search on 20 April 2011). In addition, we perused the reference lists of the identified studies and contacted trials investigators, and national and international experts in order to identify more trials for the review. We included randomised clinical trials evaluating prostaglandin E1 or E2 initiated in the perioperative period versus placebo or standard treatment for adult patients undergoing liver transplantation. We did not apply any language or publication status restrictions. Two authors independently evaluated methodological quality, ie, risk of bias of the included trials, and extracted data using standardised data extraction forms. We contacted trial investigators in attempt to retrieve information not available in the original manuscripts. We used random-effects model meta-analyses and fixed-effect model meta-analyses to estimate the odds ratio with 95% confidence interval (CI). We included ten trials in which 652 patients were randomised. The risk of bias was considered high in most trials. There was no significant effect of prostaglandins on all-cause mortality (37/298[12.4%] in prostaglandin group versus 47/312[15.1%] in control group; OR 0.84, 95% CI 0.53 to 1.37; I(2) = 0%), on primary non-function of the allograft (8/238 [3.4%] versus. 16/250[6.4%] ;OR 0.55, 95% CI 0.23 to 1.33; I(2) = 0%), and on liver re-transplantation (12/161[7.5%] versus 14/171[8.2%]; OR 0.99, 95% CI 0.44 to 2.25; I(2) = 0%). Prostaglandins seemed to significantly decrease the risk of acute kidney failure requiring dialysis (13/158[8.2%] versus 34/171[9.9%]; OR 0.37, 95% CI 0.18 to 0.75; I(2) = 0%). There was no significant increase in the risk of adverse events with prostaglandins. We found no evidence that the administration of prostaglandins to liver transplanted patients reduces the risk of death, primary non-function of the allograft, or liver re-transplantation. Prostaglandins might reduce the risk of acute kidney failure requiring dialysis, but the quality of the evidence is considered only moderate due to high risk of bias in most of the included trials. Moreover, there are risks of outcome measure reporting bias and random errors. Therefore, further randomised, placebo-controlled trials are deemed necessary.

Toxic acute hepatitis associated to the administration of prostaglandin in a dog

Prostaglandin F2? can be used in dogs to increase ejaculate volume in cases of artificial insemination, semen cryopreservation or reproductive biotechnologies. Side effects after administration of PGF2? in dogs as tachycardia, tachypnea, salivation, vomiting, diarrhea and seizures are usually dose- dependent. This paper reports the occurrence of acute toxic hepatitis after the application of PGF2? in a dog, and discusses the importance of using this drug with caution in dogs.

Early-life stress produces muscle hyperalgesia and nociceptor sensitization in the adult rat

Chronic pain in adults has been associated with early-life stress. To examine the pronociceptive effect of early-life stress, we evaluated cutaneous and muscle nociception and activity in muscle nociceptors in an animal model of neonatal stress, limited bedding, in the rat. In this neonatal limited bedding (NLB) model, litters are exposed to limited bedding between postnatal days 2 and 9, and controls to standard bedding. In adult NLB-treated rats, mechanical nociceptive threshold in skeletal muscle was significantly lower (∼22%) than in controls. Furthermore, administration of prostaglandin E 2 in skin as well as muscle produced markedly prolonged hyperalgesia, an effect prevented by spinal intrathecal injection of oligodeoxynucleotide antisense to protein kinase Cε (PKCε), a second messenger in nociceptors that has been implicated in the induction and maintenance of chronic pain. In electrophysiological studies, mechanical threshold of muscle nociceptors was reduced by ∼31% and conduction velocity significantly increased (∼28%). These findings indicate that neonatal stress induces a persistent hyperalgesia and nociceptor sensitization manifest in the adult and that the second messenger PKCε may be a target against which therapies might be directed to treat a chronic pain syndrome that is associated with early-life traumatic stress.

Acral ischemia as a presenting manifestation of essential thrombocythemia

A 74-year-old male presented with a 6-week history of rapidly progressive acral ischemia. Clinical examination revealed livid discoloration of his toes and fingertips. All peripheral pulses were palpable, and ankle brachial pressure indices were normal. Laboratory tests revealed thrombocytosis of 710,000/ll (normal range 140,000– 320,000/ll), while red blood cells were within normal range and leukocytes were moderately elevated, indicating neutrophilia but otherwise normal differential blood count. Angiography showed obliteration of all digital arteries (top right panel). There were no proximal stenoses or plaques. A cardiac source of embolism was excluded by transesophageal echocardiography. Despite intravenous and intraarterial administration of prostaglandin E1 and acetylsalicylic acid medication, the ischemic areas rapidly M. Hanoun F.-E. Brock Department of Angiology, University Hospital, University of Duisburg-Essen, Essen, Germany

Ulcerative cystitis associated with phenylbutazone administration in two horses

A 15-year-old Quarter Horse gelding and a 26-year-old Thoroughbred gelding were evaluated because of hematuria of 4 to 6 days' duration following prolonged oral administration of phenylbutazone. The horses had received either treatment with phenylbutazone for 3 months or intermittent long-term phenylbutazone treatment prior to development of hematuria. Each horse was systemically stable but had orthopedic or neurologic problems. Clinicopathologic findings included normochromic normocytic anemia in both horses and hypoalbuminemia and high BUN concentration in 1 horse. In both horses, urinalysis revealed proteinuria and RBCs, but no evidence of WBCs or bacteria. Ulceration and hemorrhage of the urinary bladder with no evidence of uroliths were observed via cystoscopy. Gastric ulceration along the margo plicatus was observed via gastroscopy. For each horse, phenylbutazone treatment was discontinued and a synthetic prostaglandin (misoprostol) was administered. The hematuria resolved, and results of a follow-up CBC, serum biochemical analysis, urinalysis, and cystoscopy 25 or 30 days after cessation of phenylbutazone treatment were unremarkable in both cases. Given the known adverse effects of NSAID treatment in several species, phenylbutazone and its metabolites were suspected to have caused ulceration of the urinary bladder, resulting in hematuria, in the 2 horses. A definitive cause of urinary bladder ulceration was not confirmed in these cases; however, resolution of ulceration after discontinuation of phenylbutazone treatment and administration of synthetic prostaglandins and exclusion of other causes suggested an association between phenylbutazone administration and ulcerative cystitis in these horses.