5-Methoxyflavone-induced AMPKα activation inhibits NF-κB and P38 MAPK signaling to attenuate influenza A virus-mediated inflammation and lung injury in vitro and in vivo.

Influenza-related acute lung injury (ALI) is a life-threatening condition that results mostly from uncontrolled replication of influenza virus (IV) and severe proinflammatory responses. The methoxy flavonoid compound 5-methoxyflavone (5-MF) is believed to have superior biological activity in the treatment of cancer. However, the effects and underlying mechanism of 5-MF on IV-mediated ALI are still unclear. Here, we showed that 5-MF significantly improved the survival of mice with lethal IV infection and ameliorated IV-mediated lung edema, lung histological changes, and inflammatory cell lung recruitment. We found that 5-MF has antiviral activity against influenza A virus (IAV), which was probably associated with increased expression of radical S-adenosyl methionine domain containing 2 (RSAD2) and suppression of endosomal acidification. Moreover, IV-infected A549 cells with 5-MF treatment markedly reduced proinflammatory mediator expression (IL-6, CXCL8, TNF-α, CXCL10, CCL2, CCL3, CCL4, GM-CSF, COX-2, and PGE2) and prevented P-IKBα, P-P65, and P-P38 activation. Interestingly, we demonstrated that 5-MF treatment could trigger activation of AMP-activated protein kinase (AMPK)α in IV-infected A549 cells, as evidenced by activation of the AMPKα downstream molecule P53. Importantly, the addition of AMPKα blocker compound C dramatically abolished 5-MF-mediated increased levels of RSAD2, the inhibitory effects on H1N1 virus-elicited endosomal acidification, and the suppression expression of proinflammatory mediators (IL-6, TNF-α, CXCL10, COX-2 and PGE2), as well as the inactivation of P-IKBα, P-P65, and P-P38 MAPK signaling pathways. Furthermore, inhibition of AMPKα abrogated the protective effects of 5-MF on H1N1 virus-mediated lung injury and excessive inflammation in vivo. Taken together, these results indicate that 5-MF alleviated IV-mediated ALI and suppressed excessive inflammatory responses through activation of AMPKα signaling.

TamaFlex™-A novel nutraceutical blend improves lameness and joint functions in working horses.

BACKGROUND: Lameness is one of the major causes of reduced physical performance and early retirement in working horses. TamaFlex™ (NXT15906F6) is a standardized synergistic anti-inflammatory botanical formulation containing Tamarindus indica seed extract and Curcuma longa rhizome extract at a 2:1 ratio. METHODS: We conducted a 12-week single-center, randomized, blinded, placebo-controlled trial demonstrating the efficacy of NXT15906F6 in horses with lameness grade 2-4 on the American Association of Equine Practitioners (AAEP) scale. Twenty-two lame horses were supplemented with NXT15906F6 (2.5 gram/day) or placebo over a period of 84 days. Improvement in lameness over placebo was the primary endpoint, and changes in the levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-cyclic citrullinated peptide (ACC-peptide) in serum, and pro-inflammatory cytokines including interleukin (IL-1ß and IL-6), tumor necrosis factor-α (TNF-α) and prostaglandin-E2 (PGE2 ) in serum and synovial fluid were the secondary endpoints. RESULTS: NXT15906F6 exhibited significant relief from lameness in a time-dependent manner. NXT15906F6 also reduced levels of ANA, PGE2 , IL-1ß, TNF-α and IL-6. Moreover, NXT15906F6 supplementation is safe and tolerable in alleviating joint pain in lame horses, and protects the joints from further degradation by reducing pro-inflammatory mediators. CONCLUSION: NXT15906F6 significantly reduces the lameness during walking and trotting, leading to an improvement in their joint flexibility, health, and working performances.

Salicylic acid-based hypoxia-responsive chemodynamic nanomedicines boost antitumor immunotherapy by modulating immunosuppressive tumor microenvironment.

The delivery of salicylic acid or its derivatives to tumor tissue in the form of nanomedicine is critical for the studies on their potential synergistic mechanism in tumor therapy and chemoprevention considering the dangerous bleeding in the high-dose oral administration. To deepen the understanding of their role in adjusting immunosuppressive tumor microenvironment (ITM), herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines (FeNCPs) via a "old drugs new tricks" strategy for synergistic chemodynamic therapy (CDT) and remodulation of ITM to elevate antitumor immunotherapy effect. PEGylated FeNCPs could be reductively cleaved to release 5-aminosalicylic acid (5-ASA) and ferric ions by azo-reductase under hypoxic conditions, which could induce tumor cell death by Fenton reaction-catalysis enhanced CDT and 5-ASA-converted carboxylquinone to promote the production of •OH. Meanwhile, cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, can promote tumor progression and immune tolerance. The released 5-ASA as a COX inhibitor could suppress the expression of PGE2, and Fe3+ was employed to reeducate M2-like tumor-associated macrophages (TAMs) to M1-like phenotype, which could initiate antitumor immune response to reach better antitumor immunotherapy. This work broadens the application of salicylic acid derivatives in antitumor immunotherapy, and provides a new strategy for their "old drugs new tricks". STATEMENT OF SIGNIFICANCE: Cyclooxygenase-2 (COX-2) and its enzymatic product prostaglandin E2 (PGE2), as immune negative regulatory molecules, facilitate the differentiation of immune cells into immunosuppressive cells to build the immunosuppressive tumor microenvironment, which can promote tumor progression and immune tolerance. Thus, down-regulation of COX-2/PGE2 expression may be a key approach to tumor treatments. Meanwhile, as a class of inhibitors of COX-2/PGE2, the potential mechanism of aspirin or 5-aminosalicylic acid has been a mystery in tumor therapy and chemoprevention. To expand the application of aspirin family nanomedicine in biomedicine, herein, we firstly developed a hypoxia-sensitive Fe-5,5'-azosalicylic acid nanoscale coordination polymer nanomedicines via a "old drugs new tricks" strategy for synergistic chemodynamic therapy and remodulation of immunosuppressive tumor microenvironment to elevate antitumor immunotherapy effect.

Hiperostosis cortical neonatal: un efecto colateral de la administración prolongada de prostaglandinas E1 / Neonatal cortical hyperostosis: a side effect of prolonged prostaglandin E1 infusion

La infusión de prostaglandinas E1 (PGE1) es habitualmente administradapor tiempos cortos para mantener la permeabilidad del ductus arterioso en lactantes con cardiopatías congénitas. En pacientes a la espera de la cirugía cardíaca el tratamiento puede prolongarse. Pueden ocurrir efectos colaterales, en su mayoría reversibles con la supresión del tratamiento. La hiperostosis cortical es una complicación frecuente de la administración prolongada de PGE1.Objetivo: Determinar la incidencia y gravedad de la hiperostosis cortical en neonatos que requieren infusión prolongada de prostaglandinas E1. Se estudiaron 61 recién nacidos con cardiopatías congénitas admitidos en la Unidad de Cuidados Intensivos Neonatales de la Clínica Bazterrica, desde enero del 2006 hasta mayo del 2010. Cinco recién nacidos recibieron tratamiento prolongado con PGE1. Cuatro presentaron evidenciaclínica y radiológica de hiperostosis cortical con elevados niveles séricos de fosfatasa alcalina. Diagnosticar esta entidad permitirá evitar estudios complementarios innecesarios o la suspensión de la cirugía cardíaca.

Prostaglandin E1 (PGE1) infusion is usually administered for short periods to maintain patency of ductus arteriosus in infants with cyanotic heart disease. Prolonged therapy may be necessary while patients are awaiting surgical treatment. Several side effects occur at the onset of the treatment, most of them reversible once the treatment is discontinued. Cortical hyperostosis is a frequent complication of prolonged PGE1 infusion. Objective is to determine the incidence and severity of cortical hyperostosis in newborn requiring prolonged prostaglandin E1 infusion. 61 newborn babies were admitted in the Neonatal Intensive Care Unit at Bazterrica Clinic, Buenos Aires City, from January 2006 to May 2010. Five newborn received prolonged PGE1 therapy defined as a longer-than-one-week treatment. Four of them had radiologic evidence of cortical hyperostosis and elevated serum alkaline phosphatase. Accurate and rapid diagnosis of this condition is critical to reduce unnecessary laboratory tests and to avoid cardiac surgery canceling.

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer.

BACKGROUND: Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). OBJECTIVES: To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer. SEARCH STRATEGY: We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008. SELECTION CRITERIA: All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models. MAIN RESULTS: Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0). AUTHORS' CONCLUSIONS: There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

Role of ATP-sensitive K+ channels in relaxation of penile resistance arteries.

OBJECTIVES: To investigate the functional presence of adenosine triphosphate (ATP)-sensitive potassium (K+) channels (K(ATP)) in penile resistance arteries by evaluating the relaxant effects of the selective K(ATP) channel openers, cromakalim and levcromakalim, and also the involvement of K(ATP) channels in the relaxation of two drugs currently used in the treatment of erectile dysfunction (ie, prostaglandin E1 [PGE1] and sildenafil). METHODS: Penile resistance arteries were dissected from the horse corpus cavernosum and mounted in microvascular myographs for isometric tension recording. The arteries were precontracted with phenylephrine, and the responses to several vasodilators were tested in the absence and presence of K+ channel blockers. RESULTS: Cromakalim and levcromakalim evoked complete concentration-dependent relaxations that were blocked by 3 microm of the selective K(ATP) channel inhibitor glibenclamide. Raising extracellular K+ (25 mM) inhibited the relaxations to PGE1 and to the selective inhibitor of the cyclic adenosine monophosphate-specific phosphodiesterase (PDE4) rolipram. At a concentration selective for calcium-activated K+(K(Ca)) channels (3 mM), tetraethylammonium inhibited rolipram responses but not those of PGE1. However, glibenclamide significantly reduced the relaxation to both PGE1 and rolipram, but not those induced by the selective inhibitor of the type 5 cyclic guanosine monophosphate-specific phosphodiesterase (PDE5). CONCLUSIONS: The present results suggest a functional role for K(ATP) channels in the relaxation of penile resistance arteries, as well as their differential involvement in the vasodilation to drugs used in the treatment of organic erectile dysfunction. They mediated relaxation to PGE1 and cyclic adenosine monophosphate-elevating agents, but not those of cyclic guanosine monophosphate-elevating agents such as sildenafil.

The incidence of pharmacologically induced priapism in the diagnostic and therapeutic management of 685 men with erectile dysfunction.

OBJECTIVE: To evaluate the incidence of pharmacologically induced priapism in the diagnostic and therapeutic management of erectile dysfunction. PATIENTS AND METHODS: Over a period of 7 years, 685 men were investigated for erectile failure. They underwent a simple test with vaso-active drugs, and the nonresponders were further investigated. Eventually, 83 men began autoinjections and 45 still continue. RESULTS: Eight (1.2%) cases of priapism presented during the simple test with vaso-active drugs in these patients, while none occurred during self-injection treatment. Three were prolonged erections induced by prostaglandin E1 (PGE1) and 5 by papaverine (Pap). Six were treated safely with intracavernosal injection of etilephrine without blood aspiration. CONCLUSION: Priapism is always a potential phenomenon where no individual, no particular drug and no specific dose are completely safe. It may be caused even with 5 microg of PGE1 or 7.5 mg of Pap. Auto-injection therapy however is a safe kind of treatment in well-experienced patients. Careful regulation of the doses and practice in the use of vaso-active drugs may reduce the priapism rate.

El uso de misoprostol asociado al tratamiento diurético en el paciente cirrótico / Misoprostol plus diuretics in the treatment of the cirrhotic patient

Es indispensable conservar la función renal de los pacientes con cirrosis hepática, ya que la insuficiencia renal se asocia con una alta morbimortalidad en dichos países. La vasoconstricción sistémica, la disminución del flujo sanguíneo renal y la disminución de metabolitos urinarios de prostaglandinas son importantes en la patogénesis de esta nefropatía. El misoprostol, prostaglandina sintética, puede modificar favorablemente algunos de los cambios en la hemodinamia renal de la cirrosis. Objetivo: Evaluar los cambios de la función renal en el paciente cirrótico con el uso de misoprostol. Metodología: se estudiaron 15 pacientes con cirrosis hepática que había desarrollado ascitis, con creatinina sérica menor a 1.5 mg/dL. Se determinaron: depuración de creatinina, volumen urinario, excreción de sodio urinario y la fracción excretada del mismo en 24 h., el filtrado glomerular y el flujo sanguíneo renal bilateral antes y después de la administración vía oral e misoprostol. Se aceptó un valor significativo a p < 0.05. resultados: Se encontró mejoría significativa únicamante en el flujo sanguíneo renal (p= 0.02), después de la administración de misoprostol. Sin embargo, al separar a los pacientes en dos grupos: los que usan diuréticos y aquellos que no los usan, se obtiene una diferencia significativa en el filtrado glomerular (p < 0.001), el flujo sanguíneo renal (p < 0.01) y la diurésis (p < 0.001). No hubo diferencias significativas en otros parámetros. Conclusiones: El uso de misoprostol en los pacientes cirróticos que utilizan diuréticos para el tratamiento de asitis y retención hídrica, mejora los parámetros de la función renal, al incrementar el flujo sanguíneo renal, el filtrado glomerular y la diuresis, actuando como vasodilatador en las arterias renales

Idiopathic arterial calcification of infancy: effectiveness of prostaglandin infusion for treatment of secondary hypertension refractory to conventional therapy: case report.

A premature baby had severe hypertension associated with idiopathic arterial calcification of infancy. Despite the fact that there was laboratory evidence of renin-mediated hypertension, the disease was refractory to specific renin antagonist and failed to respond to conventional medical treatment. Prostaglandin E1 (PGE1) infusion (dosage range 0.017-0.068 microgram/kg/min) promptly controlled hypertension on two occasions. The drug was given for a total of 65 days and then stopped after the appearance of severe thrombocytopenia; other side effects included sporadic hyperthermia and irritability. Blood pressure was then stabilized satisfactory by a multiple-antihypertensive regimen. In the light of these findings, we believe that PGE1 infusion is a possible therapeutic alternative for babies with idiopathic arterial calcification complicated by severe hypertension refractory to conventional treatment.

[Therapeutic strategy in newborn infants with multivisceral failure caused by interruption or hypoplasia of the aortic arch]. / Stratégie thérapeutique chez les nouveau-nés en défaillance multiviscérale par interruption ou hypoplasie de la crosse aortique.

Left heart obstructive lesions, in particular interrupted aortic arch or severe forms of coarctation with hypoplasia of the aortic arch, are the main cause of cardiac failure in the neonate and are often at the root of multiple organ failure which worsens the prognosis. Based on a retrospective study of 35 neonates admitted between July 1984 and June 1994, the authors attempted to identify the prognostic factors for admission to the intensive care unit and the optimal timing for operation of these patients. All neonates with a ductus-dependent aortic obstructive lesion and severe multiple (at least four) organ failure, were included in the study. There was a high mortality (54%) including firstly 7 patients who died in the three days following admission to the intensive care unit (20%); this was so-called "medical" mortality for which there was no identifiable poor prognostic factor. On the other hand, the surgical mortality (12 out of 28 cases, 43%) was significantly different in neonates operated before recovery from multiple organ failure (72%) and those operated after recovery from multiple organ failure (17%). Based on these results, the authors propose a therapeutic strategy based on prolonged preoperative intensive care until the initial multiple organ failure is reversed rather than early surgery.

Subcutaneous fat necrosis, hypercalcemia, and prostaglandin E.

We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologic studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arms, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foci of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8-10.1 mg/dl), elevated 1.25-1.25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE1 was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE1, no new lesions formed and the existing panniculitis resolved. These two cases demonstrate the association between SCFN and elevated PGE levels (endogenous in patient 1, exogenous in patient 2). No previous reports of SCFN after the administration of PGE1 have appeared in the literature.

Prostaglandin E plus famciclovir--a new concept for the treatment of severe hepatitis B after liver transplantation.

New concepts for the treatment of hepatitis B in immunocompromised patients are urgently needed. We describe our first experience with the new antiviral agent famciclovir in combination with a short course of prostaglandin E in a patient with severe hepatitis B after liver transplantation. Initial treatment with prostaglandin E reduced the inflammatory activity, as measured by transaminase activities, but did not affect viral replication. Consecutive long-term treatment with famciclovir further normalized liver function and profoundly suppressed viral replication. HBeAg and HBV-DNA -PCR all became negative and only HBsAg persisted. Histology documented marked reduction of cellular infiltration. The patient completely recovered and is back to regular work as a teacher.

Terminación de embarazo temprano con RU-486 y Ono-802: ensayo con 3 dosis diferentes de RU-486 / Termination of early pregnancy with RU-486 and ONO-802: trials with three different doses of RU-486

Según estudio multicéntrico auspiciado por la OMS, a doble ciegas, se ensayaron 3 dosis diferentes de RU-486 complementado por un análogo deprostaglandina E (ONO-802) por vía vaginal, para inducir aborto en los primeros días del embarazo. Nuestro centro estudió 99 pacientes distribuidas en 3 grupos según los tratamientos, grupo I: 200 mg de RU-486, grupo II: 400 mg de RU-486 y grupo III: 600 mg de RU-486, a todas se les colocó un supositorio vaginal de ONO-802 48 horas después. Se estudiaron aquéllas que reunían los criterios de inclusión. Se evidenció alta efectividad de este régimen para interrumpir el embarazo temprano. La eficacia fue del 93,9 por ciento en el grupo I y del 97,0 por ciento en los grupos I y II, sin diferencia significativa. Los efectos secundarios fueron escasos, sólo se destacó el dolor de bajo vientre. El sangramiento fué algo prolongado y de intensidad, fundamentalmente igual al sanggramiento menstrual, no requirió terapeútica. Se demostró que el uso del RU-486 complementado con ONO-802 es altamente efectivo para interrumpir el embarazo temprano, sin diferencias en el empleo de la dosis

Prostaglandins for the control of pulmonary hypertension in the postoperative cardiac surgery patient: nursing implications.

Right ventricular failure associated with pulmonary hypertension is a potential complication in selected cardiac surgical patients following cardiopulmonary bypass. Treatment modalities are generally focused on reduction of right ventricular afterload. PGE1 infusion is one method of providing afterload reduction by its vasodilating action on the pulmonary vasculature. Nursing management of the patient receiving PGE1 requires a thorough knowledge of the hemodynamic alterations occurring in right ventricular failure and pulmonary hypertension, as well as the effect of PGE1 on these hemodynamic parameters. The nurse must understand the rationale for concomitant administration of a vasoconstrictor with the PGE1 as well as possible methods of administering these agents. Lastly, recognition and management of possible adverse effects associated with PGE1 infusion are essential components of nursing care.

Role of prostaglandin E1 in reducing pulmonary vascular resistance in an experimental model of acute lung injury.

To determine the role and efficacy of prostaglandin E1 (PGE1) on the cardiopulmonary derangements induced by glass bead embolism, two studies were performed. In the first study, a dose response of PGE1 was tested in six animals that were first embolized with sufficient glass beads to double the pulmonary artery pressure (PAP). This study demonstrated that PGE1 reduced PAP and cardiac output by a preload-mediated mechanism, as evidenced by a reduction in the right ventricular (RV) end-diastolic segment length, at doses of 15 and 30 ng/kg.min. The second study was performed in two groups of animals, the control group (n = 6), and the treated group (n = 6), which were given PGE1 at 15 ng/kg.min after the PAP had been doubled by glass bead embolism. RV preload was kept constant. This study demonstrated that there was no difference in pulmonary vascular resistance between either the treated group or the control group. There were no other significant differences between the two groups. The results of both of these studies suggest that there is little afterload reducing effect of PGE1 in this model and at these dose ranges. Part of the mechanism of PGE1 that improves pulmonary edema and gas exchange may be the reduction of filtration surface area and hydrostatic pressures in the lungs.

Modificaciones cervicales inducidas pos prostaglandinas E2 (PGE2). Estudio doblemente ciego / Cervical changes induced by prostaglandin E2 (PGE2) double-blind study

Se llevó a cabo un estudio doblemente ciego prospectivo (placebo-testigo), para evaluar las modificaciones cervicales y la seguridad de una sola aplicación intracervical de 0.5mg de PGE2. Se estudiaron 60 pacientes en las cuales había indicación médica y obstétrica de interrupción del embarazo. En el grupo PGE2 se encontraron mayores tasas de inducciones existosas, progresión en los índices de Bishop, reducción en el trabajo de parto y en el tiempo e inducción, todo lo anterior con significado estadístico. De esta misma manera, en el grupo PGE2 hubo menor número de casos que requirieron oxitocina y cuando ésta se utilizó las dosis fueron menores. No hubo diferencia en las tasas de operación cesárea, pero se observó que en el grupo testigo la principal indicación de la operación fue cervix desfavorable; en contraste, en el grupo de estudio se encontraron otras indicaciones distintas a las de cervix desfavorable o sufrimiento fetal. Un amplio margen de seguridad se observó en madre y feto, ya que no hubo casos de sufrimiento fetal, ni diferencias en la evaluación neonatal (calificación de Apgar). Los efectos maternos fueron similares en ambos grupos, a excepción de un aumento significativo en el ácido úrico y frecuencia de polisistolia en el grupo de prostaglandina, pero sin traducción clínica. En conclusión, la prostaglandina E2 es una droga efectiva y segura para la inducción del trabajo de parto, usada a la dosis y por la vía antes mencionada

A rare gynecologic contraindication to the use of prostaglandins and oxytocin to induce abortion. A case report.

Premature rupture of the membranes was diagnosed in a 27-year-old nullipara at 24 weeks' gestation. Medical induction of abortion (because of sepsis) was attempted and failed. The products of conception were removed surgically per vagina; that procedure was followed by an intractable hemorrhage. Subtotal hysterectomy and repair of the left common iliac artery and vein were performed to stop the bleeding. In retrospect the case was diagnosed as a left ligamentary ectopic pregnancy with uterine rupture and erosion of the left common iliac vessels.

PIP: A case report of a ligamentary ectopic pregnancy that failed to respond to prostaglandin E2 for induced abortion for sepsis at 24 weeks is presented. The 27-year-old nullipara had normal ultrasound findings for gestational age up to 21 weeks gestation. She had consulted at 5 weeks for abdominal pain and bleeding, at 14 weeks again for abdominal pain, shoulder pain and vaginal bleeding, although both times the pain and bleeding resolved spontaneously. She was seen again at 16 and 21 weeks gestation, when ultrasound scans were normal for dates. At 24 weeks, she experienced vaginal discharge of blood and tissue, and was managed as premature rupture of membranes. She became septic 12 days later. She was treated with transcervical PGE2 and iv oxytocin without response for 3 days. Surgical evacuation was successful, but bleeding persisted. During laparotomy she had a large left broad ligament hematoma, a left ruptured uterus, and open left internal iliac artery and vein. These were repaired, and she received 40 units of blood, 8 platelets and 14 of plasma. Only after histology was the diagnosis of ligamentary pregnancy made. The lack of response to PG for abortion should raise suspicion of ectopic pregnancy, although preoperative diagnosis of ligamentary pregnancy is extremely rare.

Preventive and curative effects of prostaglandins on stress ulcer in rats. Application of endoscopic observation.

The present study investigated the preventive and curative effects of prostaglandins (PGs) on gastric ulcer in rats induced by physical or psychological stresses; some rats were electrically shocked, while others were exposed to affective stimuli arising from the shocked animals. The synthetic PGs dimethyl-PGE2 and rioprostil were administered orally, and their preventive effect on gastric ulceration was evaluated by determining the incidence and the ulcer index of lesions. The curative effect of drugs on ulcer healing was evaluated by determining a time-dependent change in the mucosal surface of the stomach with an endoscopic technique. Oral administration of dimethyl-PGE2 or rioprostil (25 and 50 micrograms/kg) prevented gastric ulceration significantly. Oral administration of these drugs (50 micrograms/kg, twice per day) significantly promoted the healing process of lesions 24 and 36 hr after termination of stress loading. The present results give direct evidence of the curative effect of PGs on stress ulcers and suggest that application of the endoscopic technique to the pathology of the rat's stomach may be a substantial aid in the preclinical evaluation of antiulcer drugs.

Vasodilating prostaglandins attenuate ischemic renal injury only if thromboxane is inhibited.

Ischemia-induced renal injury is prevented by inhibition of thromboxane (Tx) synthesis. This protection was believed to be secondary to a high prostaglandin (PG)/TxA2 ratio. This study tests whether increasing the PG/Tx ratio by administration of vasodilating PGs protects the reperfused ischemic kidney. Anesthetized rats underwent right nephrectomy and 45 minutes of left renal pedicle clamping. Beginning 10 minutes before clamp release, animals were treated intravenously with the following: saline placebo (n = 10); the cyclooxygenase inhibitor ibuprofen (Ibu), 12.5 mg/Kg in a bolus (n = 8); a stable analogue of prostacyclin (PGI2), 500 ng/kg/minute for 2 hours (n = 9); PGE1, 400 ng/kg/minute for 2 hours (n = 8); the combination Ibu and PGI2 (n = 8) or PGE1 (n = 8). In saline treated ischemic controls, 5 minutes after reperfusion plasma, thromboxane (TxB2) and 6-keto-PGF1 levels were 2537 and 317 pg/ml, respectively--higher than the TxB2 and 6-keto-PGF1 levels of 750 and 80 pg/ml, respectively, in nephrectomized but nonischemic sham controls (n = 7) (p less than 0.05). In ischemic control animals at 24 hours, creatinine levels were 4.6 mg/dl, relative to 0.9 ml/dl in sham animals (p less than 0.05); the weight of the left (L) ischemic kidney relative to the right (R) normal kidney was 118%, compared with 99% in sham animals (p less than 0.05); and renal histology of ischemic control animals at 24 hours showed acute tubular necrosis (ATN) relative to normal findings in sham animals. Pretreatment with Ibu led to: TxB2 and 6-keto-PGF1 levels of 116 and 40 pg/ml, lower than those of sham animals (p less than 0.05); creatinine levels of 4.6 mg/dl, L/R renal weight of 119%; and ATN similar to that of ischemic controls. Treatment with a PGI2 analogue or PGE1 was not protective and led to increases in TxB2, 6-keto-PGF1, creatinine, L/R renal weight, and ATN similar to that of ischemic controls. The combination of Ibu and either PGI2 or PGE1 led to: reduced levels of TxB2 and 6-keto-PGF1 (p less than 0.05); attenuated increases in creatinine to 2.2 and 2.3 mg/dl, respectively (p less than 0.05); and limited ATN (p less than 0.05). These data indicate that the vasodilating PG protect the ischemic reperfused kidney only when Tx is inhibited.