Dinoprostone en labor de parto: estudio clínico aleatorizado / Dinoprostone in labor: a randomized clinical trial

Objetivo: el propósito de este estudio es comparar el uso de dos preparados de prostaglandinas (dinoprostona) para la maduración cervical y alcanzar un índice de Bishop favorable, la de liberación prolongada (PROPESS) vs gel vaginal (Prostin E2)...

Desenvolvimento e validação de um método por CLAE-EM/EM para determinação de PGE2 e PGD2 em meio de cultivo celular e avaliação da recuperação das prostaglandinas utilizando diferentes condições na extração em fase sólida / Development and validation of HPLC-MS/MS method to determine PGE2 and PGD2 in cell culture medium and assessment of recovery of the prostaglandins by solid phase extraction under various conditions

Tradicionalmente, estas prostaglandinas são quantificadas por técnicas de imuno-ensaio, que apresentam diversas desvantagens. Estes metabólitos são isômeros estruturais, e dessa forma é necessário o uso de técnicas de detecção seletivas, como cromatografia líquida acoplada à espectrometria de massas sequencial (CLAE-EM/EM). Para a extração de prostaglandinas de matrizes complexas, destaca-se a extração em fase sólida (EFS), que otimizada, fornece excelentes taxas de recuperação. O objetivo deste trabalho foi desenvolver e validar um método rápido por CLAE-EM/EM, para análise simultânea de PGE2 e PGD2 de meio de cultivo celular e avaliar a eficiência de extração em diferentes condições de EFS, em relação ao método proposto pelo fabricante dos cartuchos. A separação ocorreu com coluna de fase reversa (C18, 150mm x 2.1mm, 5μm) eluída no modo gradiente com acetonitrila e água (0,1% AFO). Dez condições diferentes de EFS foram testadas. O método desenvolvido foi adequado para a análise simultânea de PGE2 e PGD2 , apresentando resolução de ~1,5 entre os picos e corrida de 11 minutos. LD da ordem de 0,5 ng/mL e LQ de 1,0 ng/mL foram obtidos para ambos os analitos. A linearidade de PGE2 e PGD2 apresentou r>0,99. Variações inferiores a 6,51% e 5,93% foram encontradas para repetibilidade e precisão intermediária, respectivamente. Foi possível diminuir perdas durante a EFS e aumentar a recuperação dos analitos. A condição que ofereceu melhor eficiência de extração aumentou o rendimento em 181% para PGE2 e 323% para PGD2 , em relação ao método proposto pelo fabricante.

PGE2 and PGD2 are very important pro-inflammatory mediators. Traditionally, these prostaglandins are estimated by immunoassay techniques, which have several disadvantages. Since these metabolites are structural isomers, it is necessary to use selective detection techniques, such as liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). For the extraction of prostaglandins from complex matrices, solid phase extraction (SPE) is an outstanding method that can be optimized to provide excellent recovery. The aim of this study was to develop and validate a rapid method for the simultaneous analysis of PGE2 and PGD2 in cell culture medium by HPLC-MS/MS and to assess the extraction efficiency of SPE under various conditions, compared to the generic method proposed by the manufacturer of the cartridges. The analytes were separated on a reversed-phase column (C18, 150mm x 2.1mm, 5μm), eluted in a gradient of acetonitrile and water (0.1% formic acid). Ten different conditions for SPE were tested. The method was suitable for the simultaneous analysis of PGE2 and PGD2 , showing a resolution of ~1.5 between the peaks and a run time of 11 minutes. LOD of 0.5 ng/mL and LOQ of 1.0 ng/mL were recorded for both analytes. The linearity of the analytical curves for both PGE2 and PGD2 showed r>0.99. Variations of less than 6.51% and 5.93% were found for repeatability and intermediate precision, respectively. It was possible to reduce the losses during SPE and enhance the recovery of the analytes. The condition affording the best extraction efficiency increased the yield by 181% for PGE2 and 323% for PGD2 , relative to the method proposed by the manufacturer.

Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K+ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K+ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E2- (PGE2, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE2) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE2) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE2; 8 µg/paw) and the ATP-sensitive K+ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE2; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.

Prostaglandin E2 and Interleukin-1beta Reduce E-cadherin Expression by Enhancing Snail Expression in Gastric Cancer Cells

Inflammation is closely related to the progression of cancer as well as tumorigenesis. Here, we investigated the effect of prostaglandin E2 (PGE2) and interleukin-1beta (IL-1beta) on E-cadherin expression in SNU719 gastric cancer cells. E-cadherin expression decreased as the dose or exposure time of PGE2 and IL-1beta increased, whereas Snail expression increased with dose or time of PGE2 and IL-1beta. E-cadherin expression reduced by PGE2 treatment increased after the transfection of Snail siRNA. Neutralization of IL-1beta using anti-IL-1beta antibody blocked the expression pattern of E-cadherin and Snail occurred by IL-1beta treatment. However, there was no synergic effect of IL-1beta and PGE2 on the expression pattern of E-cadherin and Snail. In conclusion, inflammatory mediators reduced E-cadherin expression by enhancing Snail expression in gastric cancer cells. Inflammation-induced transcriptional regulation of E-cadherin in gastric cancer has implications for targeted chemoprevention and therapy.

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil(R)), Prostaglandin E2, and Interferon-alpha as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

[Comparing the efficacy of intra-amniotic prostaglandin [PG] and oxytocin with rising induction in termination of second trimester pregnancy]

Termination of pregnancy in fetus with severe anomaly is legal in Iran. This study was done in order to compare the rate of effectiveness and complications of intra-amniotic PG and oxytocin, with rising induction in patient candidates for second trimester abortion, at Fatemieh Hospital, in Hamadan. In a randomized clinical trial study, 40 pregnant women in their second trimester with fetal CNS anomalies, were divided into two groups [N=20]. In the first group, one PG E2 Amp was injected intra-amniotic at first and then, 20 IU oxytocin was infused in 500 ml serum ringer for each patient. The infusion rate was increased up to induced effective concentrations every 15 to 30 minutes. In the second group, 50 IU oxytocin was infused with 1000 ml serum ringer and thereafter, another infusion of 50 IU oxytocin was added into the remaining 500 ml of serum. The rate of infusion was regulated on the basis of induced effective concentrations. Finally, both groups were compared for labor duration and probable side effects. The rate of success in both groups was 100%. The mean duration of labor was 19.75 +/- 5.9 hours and 30.2 +/- 6.49 hours in the group with intra-amniotic PG with oxytocin and rising induction group, respectively. This difference was statistically significant [P<0.00]. Diarrhea was seen in only one case with intra-amniotic PG injection. Differences between the frequency of side effects in both groups was not statistically significant. This study showed that the mean duration of laboring intra-amniotic PG with oxytocin method, is less than of rising induction method

Cyclooxygenase-2 Expression Is Related to the Epithelial-to-Mesenchymal Transition in Human Colon Cancers

PURPOSE: Down-regulation of E-cadherin is a hallmark of the epithelial-to-mesenchymal transition (EMT). EMT progression in cancer cells is associated with the loss of certain epithelial markers and the acquisition of a mesenchymal phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression is associated with tumor invasion and metastasis in colon cancer. This study investigated the relationship between E-cadherin and COX-2 in colon cancer cells and human colon tumors. MATERIALS AND METHODS: Colon cancer cell lines and immunohistochemistry were used. RESULTS: E-cadherin expression was inversely related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic expression of COX-2 or Snail reduced E-cadherin and induced a scattered, flattened phenotype with few intercellular contacts in colon cancer cells. Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase expression, and increased the cells' motility. In addition, exposure to prostaglandin E2 increased Snail expression and cell motility, and decreased E-cadherin expression. Membranous E-cadherin expression was lower in adenomas and cancers than in the adjacent, non-neoplastic epithelium. In contrast, the expressions of Snail and COX-2 were higher in cancers than in normal tissues and adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E-cadherin expression. Moreover, COX-2 expression was related to higher tumor stages and was significantly higher in nodal metastatic lesions than primary cancers. CONCLUSION: This study suggests that COX-2 may have a role in tumor metastasis via EMT.

comparison of efficacy and safety of vaginal misoprostol and dinoprostone for labour induction

To prove the efficacy of misoprostol for labour induction, to ascertain its safety and to determine the frequency of complications of the vaginal use. An interventional comparative study. April 2004 to March 2005. Fauji Foundation Hospital, Rawalpindi. The study was conducted for induction of labour at term by using two different kinds of labour induction agents [Dinoprostone and Misoprostol]. A total of 112 women were included in this study. With the vaginal use of these two drugs, data regarding obstetrical, fetal and neonatal outcomes was collected and analyzed. The mean induction to delivery interval was lesser in misoprostol group as compared to dinoprostone group [11.14 +/- 3.47 hrs versus 15.05 +/- 5.21hrs, p-value: <0.01]. Cesarean section rate was higher in dinoprostone group as compared to misoprostol group [30.35% vs 21.42%,]. Tachysystole and hyper stimulation were experienced more frequently in misoprostol group but was statistically insignificant [p-value: > 0.05]. The Apgar score of neonates in both groups was comparable at one minute [6.96 +/- 1.40 vs 7.18 +/- 1.08, and at 5 minutes [8.48 +/- 0.83 vs 8.66 +/- 0.64] Both misoprostol and dinoprostone appear to be effective agents for labour induction, but misoprostol has shorter induction to delivery interval, requires less oxytocin and has comparable neonatal outcomes

Cyclooxygenase-2 promotes cell proliferation, migration and invasion in U2OS human osteosarcoma cells

Osteosarcoma is the most common primary bone tumor, but the pathogenesis is not well understood. While cyclooxygeanse-2 (COX-2) is known to be closely associated with tumor growth and metastasis in several kinds of human tumors, the function of COX-2 in osteosarcoma is unclear. Therefore, to investigate the function of COX-2 in osteosarcoma, we established stable cell lines overexpressing COX-2 in U2OS human osteosarcoma cells. COX-2 overexpression as well as prostaglandin E(2) treatment promoted proliferation of U2OS cells. In addition, COX-2 overexpression enhanced mobility and invasiveness of U2OS cells, which was accompanied by increases of matrix metalloproteinase-2 and -9 (MMP-2 and -9) activities. Selective COX-2 inhibitors, NS-398 and celecoxib, inhibited cell proliferation and abrogated the enhanced mobility, invasiveness and MMP activities induced by COX-2 overexpression. These results suggest that COX-2 is directly associated with cell proliferation, migration and invasion in human osteosarcoma cells, and the therapeutic value of COX-2 inhibitors should be evaluated continuously.

Prostaglandin E2 stimulates angiogenesis by activating the nitric oxide/cGMP pathway in human umbilical vein endothelial cells

Prostaglandin E2(PGE2), a major product of cyclooxygenase, has been implicated in modulating angiogenesis, vascular function, and inflammatory processes, but the underlying mechanism is not clearly elucidated. We here investigated the molecular mechanism by which PGE 2 regulates angiogenesis. Treatment of human umbilical vein endothelial cells (HUVEC) with PGE 2 increased angiogenesis. PGE 2 increased phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), eNOS activity, and nitric oxide (NO) production by the activation of cAMP-dependent protein kinase (PKA) and phosphatidylinositol 3-kinase (PI3K). Dibutyryl cAMP (DB-cAMP) mimicked the role of PGE 2 in angiogenesis and the signaling pathway, suggesting that cAMP is a down-stream mediator of PGE 2. Furthermore, PGE 2 increased endothelial cell sprouting from normal murine aortic segments, but not from eNOS-deficient ones, on Matrigel. The angiogenic effects of PGE 2 were inhibited by the inhibitors of PKA, PI3K, eNOS, and soluble guanylate cyclase, but not by phospholipase C inhibitor. These results clearly show that PGE 2 increased angiogenesis by activating the NO/cGMP signaling pathway through PKA/PI3K/Akt-dependent increase in eNOS activity.

Role of nitric oxide and prostaglandin E2 in gastroprotection induced by lipopolysaccharide in ethanol - mediated damage in rats

This study was designed to investigate the role of endogenous nitric oxide [NO] and prostaglandin E2 [PGE2] in the gastroprotection induced by lipopolysaccharide [LPS]. Ethanol was used to induce gastric lesions in control rats and in rats pretreated with graded doses of LPS administered at different time intervals and with inhibitors of NO synthase or prostaglandin synthesis. The ethanol-induced damage on gastric mucosa was assessed by measuring the extent of the lesion. We evaluated nitrite, a breakdown of NO, and PGE2 accumulation in ex vivo gastric mucosa. The ex vivo production of both NO and PGE2 was increased in a dose-dependent manner by LPS injected 5 h before ethanol. Pretreatment with L-N6-[1-iminoethyl]lysine[dihydrochloride] inhibited the protection associated with LPS and the ex vivo increase of both NO and PGE2. Indomethacin was ineffective in suppressing LPS-mediated protection against ethanol-induced damage and in suppressing ex vivo increase of nitrite whereas the ex vivo increase of PGE2 was prevented in a dose-dependent manner. When ethanol was administered 30 min after LPS, there was a lack of protection and a lack of increase of NO and PGE2. These results indicate that the reduction in ethanol-mediated damage in LPS-treated rats depends on endogenous PGE2 formation and on endogenous NO produced by stimulation of inducible NO synthase

Comparative study of misoprostol versus dinoprostone in cervical ripening and labour induction

The aim of this study was to compare the safety and efficacy of intravaginal administered misoprostol [cytotec] versus dinoprostone pessary [prostin E2] for cervical ripening and labor induction. Sixty patients requiring induction of labor for different medical or obstetrical indications were included in this study. The misoprostol group had a significant reduction in median induction delivery time compared to dinoprostone group. There was a reduced need for the oxytocin augmentation and there was no significant difference in the mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. It was concluded that 100 mug vaginal misoprostol was a more effective induction agent than 3 mg dinoprostone vaginal pessary

Effect of Nelumbo nucifera rhizome extract on the gastrointestinal tract of rat.

Extract of Nelumbo nucifera rhizome (RNN) was used as anti-diarrheal agent to combat the diarrhea in experimental rats. The RNN extract in graded doses (100, 200, 400 and 600 mg/kg body wt.) reduced not only the frequency of defecation, wetness of fecal dropping and PGE2 induced enteropooling but also the propulsive movements of charcoal meal significantly.

Cervical ripening. A double blind controlled trial of PGE2 pessary

OBJECTIVE: To determine the efficacy of PGE2 pessary in the cervical ripening and to study its effect on other parameters of labour and delivery. DESIGN: Prospective study. SETTING: Maternity Unit II Nishtar Hospital Multan. SUBJECT: A randomized double blind trail of PGE2 pessary was carried out in patients admitted for induction of labour. MEASUREMENT AND RESULT: We looked at the change in Bishop scoring, induction delivery interval, mode of delivery and fetal outcome. Fifty% of the patients who received prostin E2 pessary went into labour before planned amniotomy while only five% of the patients receiving placebo did so. No significant difference was found in mode of delivery and incidence of fetal distress between the two groups. The shortened induction delivery interval following pre treatment with PGE2 [3 mg] pessary

Dinoprostone vs. estradiol en la inducción del parto: investigación clínica aleatorizada / Dinoprostone vs. estradiol in labor induced, randomized clinical investigation

La inducción al parto es una poderosa herramienta obstétrica de amplia aplicación, pero aún no se dispone de un procedimiento de alta eficacia para su ejecución

Dinoprostone rectal en el tratamiento de un niño con cardiopatía congénita dependiente del conducto arterioso / The use rectal E2 type prostaglandin (dinoprostone) in child with congenital heart disease

El presente informe es acerca de los resultados obtenidos al usar prostaglandinas E2 (dinoprostone) por vía rectal en un niño con persistencia del conducto arterioso. El uso de este medicamento junto con el manejo integral del paciente dio lugar a una evolución clínica satisfactoria. Los alcances de esta nueva terapéutica dependen de la investigación y experiencia que se hagan, así como de la difusión de su posible empleo, sobre todo por la posibilidad que ofrece de mantener estable un paciente, para ser trasladado al tener sospecha de este diagnóstico.

Efecto de la dinoprostona sobre la maduración cervical en enfermedad hipertensiva aguda del embarazo / Dinoprostone effect on cervical maturation in pregnant with hypertension

Objetivo. Determinar el fecto de la dinoprostona sobre la maduración cervical y la tensión arterial en una grupo de gestantes con enfermedad hipertensiva aguda del embarazo. Material y método. Se estudiaron 28 mujeres con diagnóstico de EHAE que fueron tratadas con una dosis de dinoprostona (0.5 mg intracervical). Resultados. El 67 por ciento de las mujeres mostraron aumento en el valor de Bishop (19 casos). El 50 por ciento de las mujeres tuvo indicación de cesárea por falta de progreso de trabajo de parto. La media de la tensión arterial disminuyó después de la aplicación del medicamento. Conclusión. Se obtuvo una disminución de la frecuencia de resolución por cesárea en mujeres con EHAE con relación al esperado (100 por ciento), sin incremento de riesgo para la mujer

Selective inhibition of polymorphonuclear leukocytes by immunosuppressive concentration of prostaglandin E2

Prostaglandin E2(PGE2) has been implicated as an immunosuppressive agent and plasma levels of PGE2 are elevated in patients sustaining thermal injury. We examined the effect of 10(-7) M prostaglandin E2(PGE2) on human polymorphonuclear leukocytes (PMN) to determine whether it directly inhibits stimulated responses of these cells. At this concentration, PGE2 alone was incapable of stimulating PMN intracellular hydrogen peroxide production (indirectly assayed by fluorescence of 2',7'ichlorofluorescin) or expression of the PMN CD11b/CD16 surface glycoproteins. PMN incubated in the presence of the soluble stimul phorbol myristate acetate(PMA, 100 ng/ml) or recombinant human C5a(rHC5a, 10(-8) M) generated significant amounts of hydrogen peroxide, increased their CD11b expression and decreased their CD16 expression. Pre-incubation of cells with PGE2 caused significant inhibition of all the observed changes stimulated by rHC5a. In contrast, events stimulated by PMA were not affected by preincubation of cells with PGE2. We conclude that PGE2, in concentrations identical to those found in the plasma of patients with burn injuries, is capable of selectively inhibiting some stimulated events and phenotypic expression of PMN in vitro study.

effect of prostaglandin E2 [PG E2] modulation on fracture repair: a preliminary study

Fracture repair is a complex process mediated by local regulators including PG E2. A preliminary study was undertaken on the effect of exogenous PG E2 on fracture repair to clarify the PG E2 controvarsed action of being potent bone stimulator resorbant autocoid [local hormone] aiming to reduce the morbidity of fracture healing by accelerating the healing process and shortening the repair period. fourty three male rabbits of average weight 2.0 kgms were selected and were classified into four comparable groups of ten rabbits after loss of three during the study. The control group was given daily s.c. 1 ml placebo. The PG E2 group received daily s.c. 5 ugm/kg body weight PG E2 [Dinoprostine]. L.A.S. group received daily s.c. 12.5 mg L.A.S. [Aspegic] 1kg. The PG E2-L.A.S. group received daily s.c. dose of 12.5 mgm L.A.S. and 5 U.gm. PG E2. The PG E2 dose level used showed prolonged healing period and modified repair pattern in favour of production of chondroosseouscallus with significant blood biochemical changes. This result was not apparent in the control group and was less apparent in the PG E2-L.A.S. group. It seems that the PG E2 delayed healing effect could be counteracted by L.A.S. L.A.S. group showed retarded healing process and small callus formed of thin bone trabeculae with significant blood biochemical changes. L.A.S. was not beneficial for fracture healing. In conclusion, PG E2 in the dose used was non beneficial to fracture repair and in a higher dose it could have important role in delay or non union of the fracture. This study suggest that the rate and type of bone healing activity could markedly be PG E2 dose related and dependent i.e. potent bone stimulator in small dose and bone inhibitor in higher dose

Comparación del efecto antiulceroso de la prostaglandina E2 (PGE2) y la cimetidina administrada por vía oral sobre la úlcera gástrica experimental en ratas / Comparison of antiulcerative effect of prostaglandin E2 (PGE2) and cimetidine administrated to oral via on experimental gastric ulcer in rats

Se realizó un estudio para determinar la mayor o menor efectividad por vía oral de la cimetidina respecto a la PGE2 obtenida en Cuba, para impedir la formación de úlceras pépticas en ratas, con el empleo de fenilbutazona en dosis de 200 mg/kg intramuscular. Los resultados obtenidos demostraron que el efecto antiulceroso de la cimetidina es superior al de la PGE2 en estas condiciones