Inhibition Of Prostaglandin Synthesis Research Articles

Prostaglandin-targeting agents and spectral heart rate variability in experimental partial bladder outlet obstruction in rats.

The purpose of this study was to determine the activity of the autonomic nervous system (ANS), using spectral analysis of the heart rate variability (HRV) in the model of partial bladder outlet obstruction (PBOO) in rats treated with selected non-steroidal anti-inflammatory drugs (NSAID): piroxicam (PRX) or meloxicam (MLX), and following administration of PGF2a prostaglandin analogue (Enzaprost F5). Neither the use of PGF2a analogue nor of MLX, caused significant changes in the HRV spectrum (except for HRV spectrum total power reduction with MLX). The use of PRX caused reduction of the total power and powers of all components of the HRV spectrum (except for VLF). Moreover, increased nLF and reduced nHF were observed. The obtained results suggest that the total prostaglandin synthesis block with a non-selective cyclooxygenase inhibitor (PRX) results in reduced ANS total activity, with decreased parasympathetic activity and a relative sympathetic predominance. The preferential cyclooxygenase-2 block (MLX) caused reduction of the total ANS activity as well, however with no clear disproportion of any part of the ANS. Therefore, prostaglandin synthesis inhibition and associated decrease of parasympathetic activity may constitute an additional and favourable feature of NSAID pharmacodynamics in the treatment of BPH.

Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS.

Mechanism of vascular dysfunction due to circulating factors in women with pre-eclampsia.

Circulating factors have been proposed to play a major role in the pathophysiology of endothelial dysfunction in pre-eclampsia (PE), which is defined as new-onset hypertension with proteinuria after 20 weeks of gestation. However, the mechanisms leading to altered vascular reactivity remain unclear. We hypothesized that circulating factors lead to endothelial dysfunction by increasing oxidative stress and reducing nitric oxide (NO) and prostaglandin (PG) bioavailability. Pregnant rat uterine and mesenteric arteries were incubated overnight with 3% normotensive (NP) or PE plasma collected from women upon admission to hospital. Responses to methacholine (MCh) were obtained using wire myography to assess endothelial function pathways. Vascular superoxide level was measured via dihydroethidium staining and nitric oxide synthase (NOS) expression via Western blots. PE plasma significantly increased superoxide levels and impaired endothelial dysfunction in uterine arteries (Emax 79.9±5.6% compared with 44.9±6.3%, P=0.0004), which was restored in the presence of oxidant scavengers or PG synthesis inhibition. Uterine artery vasodilation was abolished in the presence of pan-NOS inhibitor (P<0.0001) in both NP- and PE-treated vessels, but inducible nitric oxide synthase (iNOS)-dependent vasodilation was present only in NP-treated arteries. Uterine arteries exposed to PE plasma exhibit an increased endothelial NOS expression and a decreased iNOS expression. PE plasma did not alter endothelial function in mesenteric arteries, suggesting that the effect of circulating factors was vascular-bed-specific. We have shown that circulating factors lead to endothelial dysfunction via altered oxidative stress and vasodilator pathways. The present study contributes to our understanding of the pathophysiology and finding a potential target for intervention in PE.

Low dose aspirin like analgesic and anti-inflammatory activities of mono-hydroxybenzoic acids in stressed rodents

AimsTo compare analgesic and anti-inflammatory activities of aspirin and mono-hydroxybenzoic acids after their daily oral doses. Main methodsEfficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also. Key findingsAlthough stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid. SignificanceObservations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid.

Complicaciones gástricas de tratamientos farmacológicos

IntroductionGastric drug complications are one of the more adverse effects prominent and most clinically relevant, NSAIDs being the main causes. PathogenesisThe damage level gastric mucosa can be presented in different ways, being the fundamental mechanism inhibition of prostaglandin synthesis. Risk factor'sThere are several risk factors, dependent and independent, which allow to stratify patients according to their risk and, accordingly, take preventive measures. Prevention and treatmentAmong these measures, coadministration with NSAIDs proton-pump inhibitor or administration of COX-2 inhibitor have proven to be effective measures in randomized studies. However, you should evaluate other preventive and therapeutic administration of NSAIDs alternatives, mainly due to the risk. This associated cardiovascular drug group and, in particular, selective inhibitors COX-2.

The Comparative Effect of Medicinal Herb Feverfew with that of a Synthetic Parthenolide to Assess the Expression of Inducible Cyclo-oxygenase and Anti-inflammatory Activity

Aims: This paper describes the expression of inducible cyclooxygenase and anti-inflammatory of medicinal herb feverfew with a synthetic parthenolide. Study Design: In vivo model to study the expression of inducible cyclooxygenase and anti-inflammatory activity of leaf extract of T. parthenium and synthetic compound parthenolide. Place and Duration of Study: Central Research Laboratory, K. S. Hegde Medical Academy, Derlakatte, Mangalore, Karnataka, India between August 2015 and November 2015. Methodology: The inhibitory effect of COX-1 and COX -2 were assessed in the serum of mice with the treated groups of aqueous and ethanolic extract of T. parthenium (100 mg/kg) and synthetic compound parthenoilde (4 mg/kg) using Cayman’s COX activity assay kit. The anti-inflammatory activity was evaluated by Ethyl phenylpropiolate induced ear edema and carrageenan induced hind paw edema. Results: The ability of the aqueous and ethanolic extract of T. parthenium (100 mg/kg) and synthetic compound parthenoilde (4 mg/kg) to inhibit cyclooxygenase enzymes (COX-1 and COX-2) was significant when compared to control. T. parthenium leaf extracts and synthetic compound reduced the Ethyl phenylpropiolate induced ear edema and carrageenan induced hind paw edema respectively. Conclusion: The result indicates that the inhibitory effect of aqueous and ethanolic extract of T. parthenium and synthetic compound parthenoilde anti-inflammatory activity by Carrageenan induced paw edema and Ethyl phenylpropiolate induced ear edema reduced the inflammation demonstrated through the reduction of vascular permeability may be due to the inhibition of cyclo-oxygenase leading to inhibition of prostaglandin synthesis. Hence the study suggests that selected plants can be considered as a resource for searching novel anti-inflammatory agents possessing COX-2 inhibition.

Acetaminophen Prodrug: Microwave-Assisted Synthesis andin vitroMetabolism Evaluation by Mass Spectrometry

Propacetamol is an acetaminophen prodrug of intravenous administration used to control fever and pain of perioperative period in multimodal analgesia therapy. After injection, it is completely converted by plasma esterases into N,N-diethylglycine and acetaminophen, its active metabolite whose mechanism of action is the inhibition of prostaglandin synthesis. Herein, we report an improved protocol for the synthesis of propacetamol hydrochloride that allows the isolation of the active pharmaceutical ingredient (API) with high purity and yield. In addition, the in vitro metabolism of propacetamol in a microssomal reaction was evaluated by ion trap tandem mass spectrometry.

Methods of prolonging a pregnancy threatened with preterm labour

Both prolonged and shortened pregnancies carry the risk of increased mortality of the offspring. The main causes of early delivery are genetic factors, bacterial and viral infections, corpus luteum insufficiency and pathologies of the placenta. Antepartum luteolysis is due to the activity of prostaglandin F2α. A decrease in the progesterone concentration activates the sensitivity of the uterine muscles to oxytocin. Calcium ions move into the myocytes and bind to calmodulin, starting enzymatic reactions necessary for muscle contraction. Oxytocin promotes prostaglandin F2α release. Cholesterol and magnesium stimulate the binding of oxytocin to its receptors. A premature delivery is caused by a disorder of the balance between contractility and relaxation of the myometrium, which is regulated by many signalling pathways. Birth in humans can be postponed by the use of many different tocolytic medications, β-adrenergic drugs (ritodrine, hexoprenaline, fenoterol, terbutaline), magnesium salts, prostaglandin synthesis inhibitors (indomethacin, naproxen), pentoxifylline, metoprolol, calcium antagonists – calcium channel blockers (nifedipine), oxytocine antagonists (atosiban), nitric oxide donors (nitroglycerin) as well as progesterone and its synthetic analogs. In dogs and cats, in the presence of endogenous hormone deficiency, progesterone and its derivatives (gestagens) are recommended. In small animals with the risk of premature delivery, terbutaline has successfully been used. Premature delivery is a serious problem in both human and veterinary medicine, and experience from human medicine is being gradually introduced into veterinary practice.

Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

Paracetamol like antipyretic activity of lyophilized succulent of Aloe vera leaves in rats

Aims: To evaluate the antipyretic activity of lyophilized succulent of Aloe vera (AVS) as well as its interaction with conventional antipyretic drug paracetamol (PCM) against experimentally induced pyrexia in rats. Materials and Methods: Pyrexia was induced experimentally by either Brewer’s yeast or misoprostol injection after recording basal rectal temperature in rats. Animals were treated with lyophilized AVS at the dose of 100, 200, and 300 mg kg and standard drug PCM 150 mg/kg, 18 h after injection of Brewer’s yeast suspension in one set of experiment and combination of sub‑effective dose of AVS with that of PCM 1 h after injecting misoprostol in other set of experiment. Rectal temperature was recorded at different time intervals after drug administration. AVS was also phytochemically screened for the presence of tannins, saponins, flavonoids, coumarins, sterols, reducing sugar, glycosides, starch, alkaloids, and triterpenoids. Results: Pyrexia was observed at 18 h and at 1 h after Brewer’s yeast and misoprostol injection subcutaneous, respectively. AVS (200 and 300 mg/kg) treated groups showed significant fall in rectal temperature (P 0.05) with standard drug PCM at 150 mg/kg. The combination of sub‑effective dose of AVS (100 mg/kg) with that of PCM (50 mg/kg) produced significant (P < 0.05) antipyretic activity against misoprostol‑induced pyrexia at different time intervals as compared with control, AVS 100 mg/kg and PCM 50 mg/kg treated groups when used alone. Phytochemical tests showed the presence of flavonoids, saponins, tannins, reducing sugar, glycoside, starch, and steroids. Conclusion: Lyophilized AVS possesses antipyretic activity. It enhances the antipyretic activity of PCM suggesting its role in inhibition of prostaglandin synthesis.

The Beneficial Biological Properties of Salicylic Acid

Summary Salicylic acid is a phytochemical with beneficial effects on human well-being. Salicylic acid is a phenolic compound and is present in various plants where it has a vital role in protection against pathogenic agents. Natural sources include fruits, vegetables and spices. The most famous and defined effect of salicylic acid is prostaglandin synthesis inhibition. Salicylic acid has antiinflammatory effects through suppression of transcription of genes for cyclooxygenase. Most of the pharmacological properties of salicylic acid can be contributed to the inhibition of prostaglandin synthesis. Also, it was discovered that salicylic acid has other in vivo cyclooxygenase-independent pathways. Since salicylic acid does not inhibit cyclooxygenase considerably, the anti-inflammatory effect is not a consequence of direct inhibition of cyclooxygenase activity. Because of its fundamental role, it was suggested that inhibition of nuclear factor kappa B by salicylic acid is one of the key anti-inflammatory mechanisms of action for salicylates. One of the most studied properties of salicylic acid is its antioxidative activity. Salicylic acid is a confirmed inhibitor of oxidative stress. Salicylic acid is capable of binding iron. This fact is significant for antioxidative effect of salicylic acid because iron has an important function in the course of lipid peroxidation.

PAIN IN NEWBORNS. P ART II. PHARMACOLOGICAL METHODS FOR PAIN RELIEF

For the treatment of pain in patients of all age categories are widely used non-narcotic analgesics, but convincing evidence of efficacy, both non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol for the relief of pain in newborn does not exist. Antipyretic and analgesic properties of paracetamol and NSAIDs are due to inhibition of cyclooxygenase activity and the inhibition of prostaglandin synthesis. However, acetaminophen differs from NSAIDs absence of anti-inflammatory properties. An additional mechanism of action of paracetamol is the impact of its active metabolites in the endogenous cannabinoid system with a resulting decrease in anxiety, motor activity, muscle tone, decreased body temperature, decreasing symptoms of pain. In addition, the central nociceptive effect of paracetamol is associated with its effects on serotoninergic system and the influence on the transmission of nociceptive signal at the level of spinal cord. When combined with morphine, paracetamol has sparring effect. The toxic effect of paracetamol on liver cells caused by its active metabolites, which depletes the liver from glutathione, and directly damages cells in the liver, which leads to necrosis and cell death, and the subsequent development of liver failure. In newborn activity of enzymes that contribute to the formation of toxic metabolites is decreased, so they rarely develop acetamenophen-induced liver damage. It shows the relationship between the intake of paracetamol in infancy and the risk of asthma or other atopic diseases. The use of narcotic analgesics may be accompanied by respiratory depression, impaired hemodynamic, inhibition of intestinal motility. As the long-term effects of pain in the neonatal period the altered sleep-wake cycles, the development of hyperalgesia and hypersensitivity and cognitive disorders was observed. Both neonatal morphine exposure and repetitive pain have been shown to cause identical disorders: behavioral changes and abnormal learning. It is study the neuroprotective effects of dexmedetomidine, highly selective agonist of α-2 adrenergic receptors, which in combination with narcotic analgesics may minimize anesthetic-induced apoptosis and to reduce the negative influence of narcotic analgesics in the child's developing brain.

Nitric oxide, prostaglandins and angiotensin II in the regulation of renal medullary blood flow during volume expansion.

Regulation of medullary blood flow (MBF) is essential in maintaining renal function and blood pressure. However, it is unknown whether outer MBF (OMBF) and papillary blood flow (PBF) are regulated independently when extracellular volume (ECV) is enhanced. The aim of this study was to determine whether OMBF and PBF are differently regulated and whether there is an interaction between nitric oxide (NO), prostaglandins (PGs) and angiotensin II (Ang II) in regulating OMBF and PBF when ECV is enhanced. To achieve these goals, OMBF and PBF were measured by laser-Doppler in volume-expanded rats treated with a cyclooxygenase inhibitor (meclofenamate, 3mg/kg) and/or a NO synthesis inhibitor (L-nitro-arginine methyl ester (L-NAME), 3μg/kg/min) and/or Ang II (10ng/kg/min). OMBF was unchanged by NO or PGs synthesis inhibition but decreased by 36% (P < 0.05) when L-NAME and meclofenamate were infused simultaneously. PBF was similarly reduced by L-NAME (12%), meclofenamate (17%) or L-NAME + meclofenamate (19%). Ang II did not modify OMBF, but it led to a similar decrease (P < 0.05) in OMBF when it was administered to rats with reduced NO (32%), PGs (36%) or NO and PGs (37%) synthesis. In contrast, the fall in PBF induced by Ang II (12%) was enhanced (P < 0.05) by the simultaneous PGs (30%) or PGs and NO (31%) synthesis inhibition but not in L-NAME-treated rats (20%). This study presents novel findings suggesting that blood flows to the outer medulla and renal papilla are differently regulated and showing that there is a complex interaction between NO, PGs and Ang II in regulating OMBF and PBF when ECV is enhanced.

Exploration of possible mechanisms for anti-inflammatory activity of Ipomoea aquatica Forsk. (Convolvulaceae)

Currently used steroidal and non steroidal anti-inflammatory drugs have severe side effects. These side effects are very difficult to manage than the disease itself. Hence, there is to search new safe resources to cure such diseases that the use of plant based drugs. This study deals with anti-inflammatory evaluation of the hydroalcoholic extract of Ipomoea aquatica leaves as well as their possible mechanism of action. A carrageenan?induced rat paw oedema model was used for anti-inflammatory study. The mechanism/s by which Ipomoea aquatica is mediated the ant-inflammatory activity was determined by its effects in antihistamine activity, prostaglandin synthesis inhibition activity, membrane stabilizing activity and protein denaturation inhibition activity. Dose dependent anti-inflammatory activity was found with HAEIA in rat paw oedema model using carrageenan. HAEIA effective to suppressed the wheal area formed by histamine. HAEIA revealed dose dependent prostaglandin synthesis inhibition activity. HAEIA was effectively inhibited the heat induced hemolysis of HRBCs as well as heat induced albumin denaturation. Therefore, it was concluded that the HAEIA has anti-inflammatory activity possibly mediated through inhibition of release of mediator histamine and prostaglandin and has also HRBCs membrane stabilization and protein denaturation inhibition properties.

Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate.

Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility.

Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption.

Background:There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects.Objectives:We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis.Methods:Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket.Results:The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances—o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)—showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor.Conclusions:Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine-disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action.Citation:Kugathas S, Audouze K, Ermler S, Orton F, Rosivatz E, Scholze M, Kortenkamp A. 2016. Effects of common pesticides on prostaglandin D2 (PGD2) inhibition in SC5 mouse Sertoli cells, evidence of binding at the COX-2 active site, and implications for endocrine disruption. Environ Health Perspect 124:452–459; http://dx.doi.org/10.1289/ehp.1409544

Systematic Review of Preventive and Acute Treatment of Menstrual Migraine.

The aim of this systematic review is to identify the efficacy of different categories of treatments for menstrual migraines as found in randomized controlled trials or open label studies with similar efficacy endpoints. Menstrual migraine is very common and approximately 50% of women have increased risk of developing migraines related to the menstrual cycle. Attacks of menstrual migraine are usually more debilitating, of longer duration, more prone to recurrence, and less responsive to acute treatment than nonmenstrual migraine attacks. Search for evidence was done in 4 databases that included PubMed, EMBASE, Science Direct, and Web of Science. Eighty-four articles were selected for full text review by 2 separate readers. Thirty-six of the 84 articles were selected for final inclusion. Articles included randomized controlled and open label trials that focused on efficacy of acute and preventative therapies for menstrual migraine. Secondary analyses where excluded because the initial study population was not women with menstrual migraine. After final screening, 11 articles were selected for acute and 25 for preventive treatment of menstrual migraine. These were further subdivided into treatment categories. For acute treatment: triptans, combination therapy, prostaglandin synthesis inhibitor, and ergot alkaloids. For preventive treatment: triptans, combined therapy, oral contraceptives, estrogen, nonsteroidal anti-inflammatory drug, phytoestrogen, gonadotropin-releasing hormone agonist, dopamine agonist, vitamin, mineral, and nonpharmacological therapy were selected. Overall, triptans had strong evidence for treatment in both acute and short term prevention of menstrual migraine. Based on this literature search, of all categories of treatment for menstrual migraine, triptans have the most extensive research with strong evidence for both acute and preventive treatment of menstrual migraine. Further randomized controlled trials should be performed for other therapies to strengthen their use in the care of menstrual migraine patients.

Evaluation of urine fibrinogen level in a murine model of contrast-induced nephropathy.

The mechanisms of contrast-induced nephropathy are not fully understood and sensitive biomarkers of contrast-induced nephropathy are yet to be found. We investigated whether urinary fibrinogen could be a potential biomarker for contrast-induced nephropathy. To create a contrast-induced nephropathy model, mice received a prostaglandin synthesis inhibitor (indomethacin) and a nitric oxide synthase inhibitor (Nω-Nitro-L-arginine methyl ester) intraperitoneally followed by a different dose of iodixanol. In the control group, normal saline was administered. Urinary fibrinogen and serum creatinine were analyzed using enzyme-linked immunosorbent assay. Kidneys were used to quantify fibrinogen using qRT-PCR and Western blot and for histopathological examination. Histopathological examination demonstrated mild renal injury in the low-dose group, and moderate renal injury in the high-dose group. Urinary fibrinogen levels were significantly increased in an iodixanol dose-dependent manner (control vs. low-dose group, P < 0.05; control vs. high-dose group P < 0.01). Serum creatinine levels were only increased in the high-dose group (P < 0.01 compared to control), but not in the low-dose group. For fibrinogen-gene expression, in the low-dose group, Fgγ increased (qRT-PCR, Western blot, P < 0.05) in the high-dose group, Fgβ and Fgγ decreased (qRT-PCR, P < 0.01; Western blot, P < 0.05), and Fgα increased (qRT-PCR, P < 0.05; Western blot, P < 0.05). We propose that urinary fibrinogen could be used as a potential biomarker for early contrast-induced nephropathy diagnosis.

7B.02

Objective: Approximately 25% of hypertensive patients >65 years are treated for arthrosis, which is the most common cause of long term use of non-steroidal anti-inflammatory drugs (NSAID). NSAID inhibits prostaglandin synthesis and interacts with the renin angiotensin system. The objective of this study was to investigate if concomitant use of NSAID in hypertensive patients is associated with a lower possibility to reach target blood pressure <140/90 mm Hg, and to elucidate if there are gender differences regarding this matter.Design and method: This cross-sectional cohort study includes 40825 patients with hypertension from the Swedish primary Care Cardiovascular Database (SPCCD) in 2007–2008. Patient characteristics, antihypertensive drug class, dispensations of NSAIDs, comorbidities and blood pressure measurements were analyzed. The proportion of days covered (PDC) with prescription was calculated in order to analyze the NSAID use and the PDC was grouped <50%, 50–80% and >80% of days covered with prescription during 180 days prior to the last blood pressure measurement. Results: In all 6700 patients had at least one prescription of NSAID. Patients with NSAID were younger (67.9 ± 11.2 vs 69.4 ± 11.9 years, p < 0.0001), and more often female (63.2 vs 56.3%, p < 0.0001) with a diagnosis of musculoskeletal disease (20.8 vs 12.8%, p < 0.0001 and with no cardiovascular comorbidity (26.5 vs 32.1%, p < 0.0001). There was no difference in SBP between patients with and without NSAID (142 ± 16, 142 ± 17 mmHg respectively, ns). Patients with NSAID had a higher DBP (80 ± 10, 79 ± 10 mmHg, respectively p < 0.001). In a logistic regression model adjusted for age, smoking, cardiovascular comorbidity, antihypertensive drug class, education, and country of birth there was no difference in the proportion achieving target blood pressure in patients with and without concomitant use of NSAID irrespective of the PDC for NSAID users (figure 1). The results were similar in both genders. Conclusions: Concomitant use of NSAID in hypertensive patients does not seem to be associated with a higher blood pressure level. The use of NSAIDs is not associated with a reduced ability of achieving target blood pressure. Thus, hypertensive patients do not à priori need to be discouraged to use NSAID.

Prostanoids and NSAIDs in cardiovascular biology and disease.

Prostanoids and related arachidonic acid derivatives are important physiologic modulators in arteries, as well as mediators of inflammation, hemostasis, and cell proliferation. Their participation in atherosclerosis and in acute thrombotic events is complex, as demonstrated by untoward cardiovascular (CV) effects associated with clinical use of inhibitors of prostaglandin synthesis for treatment of chronic pain, inflammatory states, or cancer prophylaxis. Newer understanding of the pathophysiology of atherosclerosis and the pharmacology of prostanoids promises potential resolution of current problems resulting from the hazards of available prostanoid-altering drugs.