Reduced platelet aggregation in women after intercourse: a possible role for the cyclooxygenase pathway.

We hypothesise that molecules in the cyclooxygenase pathway affect platelet activity when seminal fluid (SF) is present. We considered the influence of SF on platelet aggregation in women, and believe that the prostanoids in SF signalling are significant. Thirty-one female subjects were studied, 20 of whom were sexually active. Male partners were given either aspirin or indomethacin to inhibit cyclooxygenase. The 6-keto prostaglandin F1α (6-keto PGF1α) and prostaglandin E metabolite (PGE-M) in SF were measured by competitive assay. Platelets and prostanoids were evaluated in women, periodically, before and after intercourse. The platelets were tested with adenosine diphosphate (ADP) and arachidonic acid (AA). To block the interaction between the uterus and SF, some couples used condoms. We found that the 6-keto prostaglandin F1α in urine at 2 hours post-intercourse (1418.75 pg/mL, Std 688.39) was greater than pre-intercourse (772.68 pg/mL, Std 116.54). Post-intercourse, a transient decrease in platelet aggregation was observed in women whose partners did not use condoms. Averages for platelet aggregation were 20.16% with ADP, and more significantly, 37.79% with AA after 2 hours. In contrast, couples using condoms showed no changes, averaging 64.02% with ADP and 72.06% with AA. Women whose partners were taking aspirin or indomethacin also showed no changes. SF from men taking aspirin or indomethacin led to no reduction in platelet aggregometry in their partners. These results indicate that in cases of exposure to SF, the transient change in women's platelet activity could be related to the cyclooxygenase pathway.

Management of constipation in Parkinson's disease.

INTRODUCTION: Constipation is a frequent non-motor feature of Parkinson's disease (PD). It is the most common gastrointestinal symptom of the disease and it can precede motor symptoms by as much as 20 years. Constipation can produce discomfort and affect activities of daily living, productivity and quality of life, thus warranting early diagnosis and treatment. AREAS COVERED: In this review, the safety and efficacy of traditional and novel strategies for constipation management will be discussed. A treatment algorithm for constipation in PD will be presented. EXPERT OPINION: Polyethylene glycol and lubiprostone are first-line compounds recommended by evidence-based medicine guidelines for the treatment of constipation due to slow colonic transit in PD. Management of constipation secondary to defecatory dysfunction due to pelvic floor dyssynergia can be done by levodopa or apomorphine injections, botulinum toxin type A injection into the puborectalis muscle, and nonpharmacological interventions, like biofeedback therapy or functional magnetic stimulation, which showed some benefit in PD patients with constipation, but in general more extensive studies are warranted.

Prostaglandins for adult liver transplanted patients.

BACKGROUND: 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. OBJECTIVES: To assess the benefits and harms of prostaglandin E1 or E2 in adult liver-transplanted patients. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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). MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

[Pharmacological treatment of the irritable bowel syndrome: a technical review]. / Tratamiento farmacológico del síndrome de intestino irritable: revisión técnica.

INTRODUCTION: The goal of a comprehensive treatment in irritable bowel syndrome (IBS) patients should be the improvement of symptoms and improve the quality of life. AIM: To review the drugs recommended in IBS, their mechanisms of action, side effects, risks and benefits, contraindications, availability in our country and the evidence supporting their use. MATERIAL AND METHODS: A technical and narrative review which evaluated the articles published in national and world literature regarding the pharmacological treatment of IBS was performed. PubMed and IMBIOMED electronic databases were searched (until September 2009) using all descriptors regarding IBS and drug therapy. RESULTS: There is enough clinical evidence to recommend the use of antispasmodics (alone orin combination) and tricyclic antidepressants for pain treatment in IBS. Laxatives are useful in the management of chronic constipation, but there is little evidence in the management of IBS. Although, antiflatulents and antidiarrheals are widely used there is little information supporting its use. The use of a nonabsorbable antibiotic (rifaximin) is effective in a subgroup of IBS patients. Serotoninergics drugs have proven effective in relieving symptoms of IBS; however, these drugs require caution in their use. There are studies have shown that probiotics improve some symptoms of IBS. CONCLUSIONS: There are many effective treatment options in the symptomatic management of IBS. The choice of treatment should be based on the predominant symptoms of each patient.

The localization of PGE2 receptor subtypes in rat retinal cultures and the neuroprotective effect of the EP2 agonist butaprost.

It is concluded from immunohistochemical that all four types of prostaglandin-E(2) (PGE(2)) (EP1, EP2, EP3 and EP4) receptors are associated with specific cell-types in primary rat retinal cultures. Analysis specifically of EP2 receptor immunoreactivity shows it to coexist with some neurones expressing Thy-1 and calbindin immunoreactivities as well as with vimentin-positive Müller cells. Moreover, exposure of cultures to the EP2 specific agonist butaprost (100 nM) for a period of 24h results in a generation of cAMP thus providing support for the functionality of EP2 receptors. Cell survival was significantly affected in cultures where the serum concentration was reduced from 10 to 1% for 24h. This was reflected by a reduction in the number of GABA-positive neurons and an elevation of released lactate dehydrogenase (LDH) into the culture medium. Moreover, a number of cells displayed a clear generation of reactive oxygen species (ROS) and a staining for the breakdown of DNA by the TUNEL procedure as an indicator for apoptosis. These negative effects were attenuated when butaprost (100 nM) was present during the serum reduction and 30 min before the insult. The present studies provide evidence to show that all PGE(2) receptor types exist in the retina of rat pups, remain functional when the retinal cells are cultured and that specific activation of EP2 receptors with butaprost can attenuate a detrimental insult caused by insufficient serum that may occur in situ by reduced trophic support.

Embarazo a terminó: inducción del parto con prostaglandina E1 y prostaglandina E2 / Pregnancy to term: labor induction with prostanglandin E1 and prostandin E2

Se presenta un estudio descriptivo, prospectivo, para comparar la eficacia, seguridad y los costos de los análogos sintéticos de prostaglandina (misoprostol y dinoprostona) en la inducción del trabajo de parto en pacientes con embarazos a término, con indicación de inducción e índices de Bishop menores de 7 puntos. Las pacientes fueron distribuidas al azar en dos grupos, para recibir 50 ug de misoprostol intravaginal cada tres horas por seis dosis dinoprostona 0,5 mg intracervical cada seis horas por tres dosis. El grupo que recibió misoprostol, requirió menor número de dosis, presentó menor duración del trabajo de parto y mayor número de partos instrumentales. Ambos medicamentos son similares en seguridad, siendo el misoprostol de menor costo. Se concluyó que el misoprostol intravaginal es más efectivo, económico e igualmente seguro que la dinoprostona intracervical, recomendándose su uso en la inducción del trabajo de parto en embarazo a término con índice de Bishop desfaborables

Biologically significant physico-chemical properties of antioxidative prostaglandin derivatives.

A monomeric derivative and several oligomeric derivatives were synthesized from prostaglandin B2. Their lipid solubility was studied by measuring their octanol-water partition coefficients. With EPR spectroscopy, the oligomeric derivatives were shown to have g = 2 signal, indicating these compounds have intrinsic free radicals. Measuring the rate of adenochrome formation, it was shown that these derivatives could scavenge superoxide anions. Using a spin-trapping technique employing DMPO, we found that these oligomers could also scavenge hydroxyl radicals. The calcium chelating activity of these compounds were also studied. In an in vitro rat model, these compounds inhibited lipid peroxidation as measured by the production of thiobarbituric acid reacting substances. Other prostaglandin oligomeric derivatives synthesized from PGE1 were also studied, and their properties were compared with these new compounds. Results suggest that both the water solubility and the chelating activity for calcium ions may not be related to their protective effects in ischemic or traumatic injury.

[Prophylactic effect of Misoprostol on gastric lesions induced by aspirin (ASA) in healthy subjects]. / Efecto profiláctico de Misoprostol sobre las lesiones gástricas inducidas por aspirina (AAS) en sujetos sanos.

Aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs), are extensively used for treating rheumatic diseases, inflammatory problems, and pain of different etiologies. However, their use is limited by the damage they may produce to the gastroduodenal mucosa. The purpose of this double-blind, multicenter, randomized, placebo-controlled study was to assess and corroborate the protective effect of misoprostol on the gastric mucosa against ASA injury. Following endoscopic screening, 60 healthy male and female subjects were assigned, at random, to one of two treatment groups. One group was treated with ASA (3.0 g/day, in three divided doses) and misoprostol (600 mcg/day, co-administered with ASA); the other with ASA and placebo. After six days of treatment, endoscopy was repeated and the gastric mucosa was graded on a 5 point endoscopic score. Protection was defined as mucosa having an endoscopic score of 2 or less (10 or fewer hemorrhages or erosions). Misoprostol produced a significant (p = 0.005) and profound protection of the gastric mucosa against ASA injury and was well tolerated. These results suggest that misoprostol should have significant therapeutic utility in the treatment and prevention of gastropathy due to NSAIDs.

Inhibition of ischemic brain edema formation by post-ischemic administration of a prostaglandin oligomer.

We studied the efficacy of an oligomeric derivative of prostaglandin E1 in protecting the rat brain against focal ischemia. The degree of ischemic damage was evaluated from three parameters, namely, the degree of edema formation, reduction of motor performance, and memory disturbance as measured by a passive avoidance test. The pre-ischemic administration of the drug (6 mg/kg i.p.) had some effects, but the differences were not significant. The post-ischemic administration (6 mg/kg i.p.) produced significant improvement in all three parameters. The increase of water content of the ischemic hemisphere was reduced (p less than 0.05); the total motor score was improved (p less than 0.01); and the memory disturbance as estimated by the passive avoidance test was reduced (p less than 0.01). A possible mechanism of protection is discussed.

Cytoprotective effect of S-adenosylmethionine compared with that of misoprostol against ethanol-, aspirin-, and stress-induced gastric damage.

The administration of oral S-adenosylmethionine (SAMe) (100 mg/kg body weight) was well tolerated by the rat gastroduodenal tract. Moreover, rats given SAMe exhibited a significant increase in non-protein sulfhydryl groups of gastroduodenal mucosa as compared with control animals. The abilities of SAMe and misoprostol, a prostaglandin E1 analogue, to protect the gastric mucosa against necrosis induced by various noxious stimuli (ethanol, aspirin, stress) were also compared in standardized, experimental rat models. Pretreatment with SAMe or misoprostol significantly and to the same extent reduced gastric mucosal injury. The experiments described herein indicate that SAMe, a molecule used for the treatment of osteoarthritis, can exert a gastric cytoprotective effect in animals. As preliminary data have shown that this effect may also be reproduced in humans, SAMe seems to provide a therapeutic advantage, in contrast to currently available nonsteroidal anti-inflammatory agents.

Proteçäo da mucosa G. I. pelo misoprostol em pacientes com artrite reumatóide fazendo uso de cetoprofeno / G. I. mucosa protection with misoprostol in patients with rheumatoid arthritis and using ketoprofen

Foi realizado um estudo aberto, näo comparativo, para avaliar a eficácia do Misoprostol (prostaglandina E1) no tratamento de 29 pacientes portadores de sintomatologia do trato gastrintestinal superior produzida por Cetoprofeno no tratamento da artrite reumatóide. O estudo foi previsto para um período máximo de oito semanas com avaliaçöes clínicas ao final da 2ª, 4ª e 8ª semanas. Na 2ª semana de tratamento, 27(93,1%) dos pacientes referiram diminuiçäo acentuada ou ausência dos sintomas gastrintestinais, mostrando um efeito rápido e eficiente do Misoprostol administrado 200mcg, três vezes ao dia, em "co-uso" com Cetoprofeno. Apenas seis pacientes tiveram efeitos colaterais, sendo diarréia o relato mais freqüente, que cedeu sem a interrupçäo do Misoprostol

O misoprostol no tratamento da úlcera duodenal / Misoprostol in the treatment of duodenal ulcer

Realiza-se um estudo aberto, objetivando avaliar os efeitos terapêuticos do Misoprostol, um derivado metilado da PGE1, na cicatrizaçäo da úlcera duodenal. Assim, foram tratados 20 indivíduos, 19 do sexo masculino e um do feminino, portadores de úlcera duodenal ativa, diagnosticada pela endoscopia. Cada paciente recebeu o Misoprostol em comprimidos, na posologia de 400 mcg duas vezes ao dia, por um período de quatro semanas. Concluído o ensaio, foi registrado um índice de cicatrizaçäo de 100%, baseado na cicatrizaçäo total da(s) úlcera(s) comprovada pela endoscopia. Os controles clínicos efetuados nos 14ª e 28ª dias de tratamento demonstraram remissäo dos sintomas, notadamente da dor, em 80% e 100% dos casos respectivamente. As reaçöes adversas representadas basicamente por aumento do número de evacuaçöes ou diarréia em 13 pacientes (65%) em nenhum momento teve significado clínico e nem mesmo obrigou à interrupçäo da medicaçäo. Conclue-se que, com base nos resultados, que o Misoprostol, na dose de 400 mcg duas vezes ao dia, durante (quatro) semanas, é uma droga segura e plenamente eficaz para a cicatrizaçäo da úlcera duodenal

[Duodenal ulcer and risk factors: influence of the treatment with misoprostol]. / Ulcera duodenal (U.D.) e fatores de risco: influência do tratamento com misoprostol.

Two hundred and thirty five duodenal ulcer patients agreed to be treated with Misoprostol 400 mcg b.i.d. during four weeks. The influence of cigarette smoking, alcohol and coffee on the healing rate were determined. Endoscopic examinations were performed at the beginning of the study and after four weeks of treatment. Clinical evaluations were done at the beginning and after two and four weeks of treatment. According to the type of cohort the healing rate after four weeks of treatment was: a) 70.6% when all 235 patients intended to be treated were considered; b) 77.9% when all patients reexamined after four weeks + 5 withdrawn because of side effects (3) or worsening of symptoms (2) where analysed and, c) 79.8% when only the 208 patients that completed four weeks of treatment were considered. Loosen stools or diarrhea were observed in 37% of the patients but only in 2 (0.85%) severe diarrhea resulted in interruption of the treatment. The healing rates were not altered by the use of cigarettes, alcohol or coffee, suggesting that Misoprostol probably inhibited the deleterious effects of those risk factors.

[Misoprostol and cimetidine in the treatment of active duodenal ulcer. Multicenter, double-blind, clinico-endoscopic study. The Argentine experience]. / Misoprostol y cimetidina en el tratamiento de la úlcera duodenal activa. Estudio clínico-endoscópico, multicéntrico, doble ciego. Experiencia Argentina.

Ten Argentine centers participated in this cooperative trial. One hundred and sixteen patients with endoscopically proven duodenal ulcer entered the study and were randomly assigned to receive either Misoprostol 800 micrograms or Cimetidine 1200 mg, q.i.d. per day, during four weeks of treatment. Patients were allowed to take Amphogel tablets for relief of ulcer pain when necessary, and clinical, lab-tests and adverse effects were evaluated weekly. Ninety-nine patients (Misoprostol 54, Cimetidine 45) completed the study and were evaluable. Success/failure criteria were based on endoscopically documented complete healing at the end of treatment period. Healing rate of four week was 85.2 per cent (46/54) for Misoprostol and 75.5 per cent (34/45) for Cimetidine, with no statistically significant difference. It is concluded that Misoprostol and Cimetidine are highly effective and safety in the healing of active duodenal ulcer. Misoprostol is a new therapeutical alternative for the treatment of duodenal ulcer patients.

Gastric cytoprotection induced by prostaglandin-dopaminergic mechanism.

The cytoprotective effects on the gastric mucosa of the Bromocriptine, a peripheral dopaminergic receptor agonist compared with Misoprostol against ethanol-induced injury were studied. Pretreatment with SCH 23390 (a DA1 receptor antagonist) and Domperidone (a DA2 receptor antagonist), showed that Misoprostol was peripheral dopaminergic receptor dependent in the gastric cytoprotective mechanism, and that Bromocriptine was a selective peripheral DA2 receptor agonist in the gastric cytoprotection mechanism; as well as, indomethacin pretreatment, showed that peripheral DA2 receptors were endogenous prostaglandin dependent. In conclusion, a prostaglandin-dopaminergic mechanism was postulated in gastric cytoprotection.

[A double-blind study with misoprostol in the treatment of active duodenal ulcer]. / Estudio doble ciego con misoprostol en el tratamiento de la úlcera duodenal activa.

Misoprostol (Mi, a double blind study in the treatment of active duodenal ulcer (DU). The purpose of the paper was to evaluate the effect of Mi vs. Placebo (Pl) without antacids, assessing at the same time side effects and histological alterations. Thirty five patients with active DU diagnosed by endoscopy and photography (performed on days, 0, 14 and 28) were studied. They received 4 doses/day of Mi 100 mcg, or Pl double blind. In each control, biochemical studies in blood and urine were performed. Acetaminophen, 500 mg was the only analgesic allowed. Six patients were excluded. Of the remaining 29 patients, 15 received Mi and 14 Pl. There was no difference in healing at the 14 day stage. At the 28 day stage there was complete healing of the ulcer in 66.6%, and reduction of the ulcer diameter of 89% those who received Mi. The healing rate was 28.5% and reduction of the ulcer diameter of 31% on those patients who received placebo. There were no biochemical alterations or side effects. There was no significative difference between biopsies taken from pylorus and antrum. The consumption of acetaminophen was similar to both groups. It is concluded that Mi has a healing effect similar to H2 blocking agents, accelerating the healing of active DU, without side effects and biochemical changes.