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Effect of chlorella supplementation on systematic symptoms and serum levels of prostaglandins, inflammatory and oxidative markers in women with primary dysmenorrhea.
Haidari, F, Homayouni, F, Helli, B, Haghighizadeh, MH, Farahmandpour, F
European journal of obstetrics, gynecology, and reproductive biology. 2018;:185-189
Abstract
OBJECTIVE Primary dysmenorrhea is one of the most commonly reported disorders for women that have unfavorable effects on patient's quality of life. Based on the evidences that suggest the anti-inflammatory and analgesic properties of chlorella, this double-blind, randomized, placebo controlled clinical trial aimed to evaluate the effects of Chlorella supplementation on the severity of menstrual pain in a group of young women with primary dysmenorrhea. STUDY DESIGN In this clinical trial, 44 girls with primary dysmenorrhea were randomly divided into intervention and control groups. Patients in the intervention group received 1500 mg/day of chlorella as 5 soft gel and the control group received placebo soft gels for eight weeks. Menstrual and food information were collected using a previously validated and published questionnaire. Anthropometric measurements and biochemical parameters including prostaglandin E2 (PGE2), ProstaglandinF2a (PGF2a), high-sensitivity C-reactive protein (hs-CRP) and malondialdehyde (MDA) were assessed at baseline and end of week eight. RESULTS In chlorella supplemented group the PGE2, PGF2a, hs-CRP and MDA decreased significantly (P < 0.05). The severity and duration of dysmenorrheal pain were significantly reduced in the intervention group compared to the control group (p < 0.05). Systemic symptoms of dysmenorrhea (fatigue, headache, nausea, vomiting, lack of energy) decreased in the chlorella group (p < 0.05). The mean of menstrual characteristics, anthropometric indices and daily energy and macronutrient intake in both intervention and control groups were not changed significantly. CONCLUSION This study showed that chlorella supplementation could decrease the severity of pain and systemic symptoms and improve serum levels of prostaglandins, inflammatory and oxidative markers in women with primary dysmenorrhea.
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Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.
O'Connor, MG, Thomsen, K, Brown, RF, Laposata, M, Seegmiller, A
Prostaglandins, leukotrienes, and essential fatty acids. 2016;:46-49
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Abstract
BACKGROUND Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). METHODS This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. RESULTS Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. CONCLUSIONS Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation.
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Acute effects of dipyrone on renal function in patients with cirrhosis: a randomized controlled trial.
Zapater, P, Llanos, L, Barquero, C, Bellot, P, Pascual, S, Carnicer, F, Palazón, JM, Gimenez, P, Esteban, A, Llorca, L, et al
Basic & clinical pharmacology & toxicology. 2015;(3):257-63
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Abstract
Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.
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Roles of nitric oxide and prostaglandins in the hyperemic response to a maximal metabolic stimulus: redundancy prevails.
Lopez, MG, Silva, BM, Joyner, MJ, Casey, DP
European journal of applied physiology. 2013;(6):1449-56
Abstract
Vasodilatory mechanisms controlling post-exercise or post-ischemic hyperemia are thought to be under redundant control and remain incompletely understood. A maximal metabolic stimulus evoked by ischemic exercise (IE) might limit redundancy by full activation of multiple pathways. We tested whether nitric oxide (NO) and/or prostaglandins contribute to the hyperemic response to IE. 17 subjects were randomized into two groups and performed three trials of IE during control (saline), N (G)-monomethyl-L-arginine (L-NMMA; NOS inhibition) (protocol 1) or ketorolac (cyclooxygenase inhibition) infusion (protocol 2), and combined L-NMMA/ketorolac infusion via a brachial arterial catheter. Forearm blood flow (FBF) was measured with venous occlusion plethysmography following IE trials consisting of 5 min of ischemia and simultaneous rhythmic handgrip exercise (final 2 min). Peak and total (area under the curve) FBF and blood pressure (MAP) were measured for 3 min after each trial. Forearm vascular conductance (FVC) was calculated as FBF/MAP. Change (Δ) in peak FBF and FVC from baseline differed only between peak FBF for the saline and L-NMMA + ketorolac trials in protocol 1. Peak ΔFBF was 26.8 ± 2.5, 30.0 ± 2.8, and 33.9 ± 3.6 ml 100 ml(-1) min(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials (P = 0.04). For protocol 1 (n = 8), total ΔFVC was 59.6 ± 4.3, 57.8 ± 6.0, and 59.9 ± 5.6 ml 100 ml(-1) 100 mmHg(-1) for saline, L-NMMA, and L-NMMA + ketorolac trials, (P = 0.82). For protocol 2 (n = 9), total ΔFVC was 54.2 ± 5.0, 56.9 ± 4.5, and 56.5 ± 5.3 ml 100 ml(-1) 100 mmHg(-1) for saline, ketorolac, and ketorolac + L-NMMA trials, (P = 0.69). These results suggest that NO and PGs are not obligatory for the hyperemic response to IE, and other vasodilator mechanisms predominate.
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Impaired acetylcholine-induced cutaneous vasodilation in young smokers: roles of nitric oxide and prostanoids.
Fujii, N, Reinke, MC, Brunt, VE, Minson, CT
American journal of physiology. Heart and circulatory physiology. 2013;(5):H667-73
Abstract
Cigarette smoking attenuates acetylcholine (ACh)-induced cutaneous vasodilation in humans, but the underlying mechanisms are unknown. We tested the hypothesis that smokers have impaired nitric oxide (NO)- and cyclooxygenase (COX)-dependent cutaneous vasodilation to ACh infusion. Twelve young smokers, who have smoked more than 5.2 ± 0.7 yr with an average daily consumption of 11.4 ± 1.2 cigarettes, and 12 nonsmokers were tested. Age, body mass index, and resting mean arterial pressure were similar between the groups. Cutaneous vascular conductance (CVC) was evaluated as laser-Doppler flux divided by mean arterial pressure, normalized to maximal CVC (local heating to 43.0°C plus sodium nitroprusside administration). We evaluated the increase in CVC from baseline to peak (CVCΔpeak) and area under the curve of CVC (CVCAUC) during a bolus infusion (1 min) of 137.5 μM ACh at four intradermal microdialysis sites: 1) Ringer (control), 2) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor), 3) 10 mM ketorolac (COX inhibitor), and 4) combination of l-NAME + ketorolac. CVCΔpeak and CVCAUC at the Ringer site in nonsmokers were greater than in smokers (CVCΔpeak, 42.9 ± 5.1 vs. 22.3 ± 3.5%max, P < 0.05; and CVCAUC, 8,085 ± 1,055 vs. 3,145 ± 539%max·s, P < 0.05). In nonsmokers, CVCΔpeak and CVCAUC at the l-NAME site were lower than the Ringer site (CVCΔpeak, 29.5 ± 6.2%max, P < 0.05; and CVCAUC, 5,377 ± 1,109%max·s, P < 0.05), but in smokers, there were no differences between the Ringer and l-NAME sites (CVCΔpeak, 16.8 ± 4.3%max, P = 0.11; and CVCAUC, 2,679 ± 785%max·s, P = 0.30). CVCΔpeak and CVCAUC were reduced with ketorolac in nonsmokers (CVCΔpeak, 13.3 ± 3.6%max, P < 0.05; and CVCAUC, 1,967 ± 527%max·s, P < 0.05) and smokers (CVCΔpeak, 7.8 ± 1.8%max, P < 0.05; and CVCAUC, 1,246 ± 305%max·s, P < 0.05) and at the combination site in nonsmokers (CVCΔpeak, 15.9 ± 3.1%max, P < 0.05; and CVCAUC, 2,660 ± 512%max·s, P < 0.05) and smokers (CVCΔpeak, 11.5 ± 2.6%max, P < 0.05; and CVCAUC, 1,693 ± 409%max·s, P < 0.05), but the magnitudes were greater in nonsmokers (P < 0.05). These results suggest that impaired ACh-induced skin vasodilation in young smokers is related to diminished NO- and COX-dependent vasodilation.
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Comparative impact on prostanoid biosynthesis of celecoxib and the novel nonsteroidal anti-inflammatory drug CG100649.
Skarke, C, Alamuddin, N, Lawson, JA, Cen, L, Propert, KJ, Fitzgerald, GA
Clinical pharmacology and therapeutics. 2012;(6):986-93
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Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate cardiovascular risk by disrupting cyclooxygenase-2 (COX-2)-dependent biosynthesis of prostacyclin (PGI(2)). CG100649 is a novel NSAID proposed to inhibit both COX-2 and carbonic anhydrase (CA)-I/-II. We compared its impact on prostanoid biosynthesis with that of celecoxib, an NSAID purposefully designed to selectively inhibit COX-2. In a controlled, double-blind randomized trial, single oral doses of 2 or 8 mg CG100649, 200 mg celecoxib, or placebo were well tolerated by healthy volunteers (n = 23). Both CG100649 and celecoxib had the effect of depressing urinary excretion of 2,3-dinor-6-keto-PGF(1α) (PGI-M); the effect of CG100649 was dose-dependent and more sustained (up to 240 h after the dose) than that of celecoxib. Neither CG100649 nor celecoxib significantly inhibited COX-1-dependent prostanoid formation. CA inhibition was not detected after administration of CG100649, despite its partitioning asymmetrically into erythrocytes. CG100649 and celecoxib are both relatively selective inhibitors of COX-2, but they differ in duration of action. Whether they have similar impact on cardiovascular events remains to be determined.
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Combined inhibition of nitric oxide and vasodilating prostaglandins abolishes forearm vasodilatation to systemic hypoxia in healthy humans.
Markwald, RR, Kirby, BS, Crecelius, AR, Carlson, RE, Voyles, WF, Dinenno, FA
The Journal of physiology. 2011;(Pt 8):1979-90
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Abstract
We tested the hypothesis that nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute independently to hypoxic vasodilatation, and that combined inhibition would reveal a synergistic role for these two pathways in the regulation of peripheral vascular tone. In 20 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to steady-state (SS) isocapnic hypoxia (O₂ saturation ~85%). All trials were performed during local α- and β-adrenoceptor blockade (via a brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatory mechanisms. The individual and combined effects of NO synthase (NOS) and cyclooxygenase (COX) inhibition were determined by quantifying the vasodilatation from rest to SS hypoxia, as well as by quantifying how each inhibitor reduced vascular tone during hypoxia. Three hypoxia trials were performed in each subject. In group 1 (n = 10), trial 1, 5 min of SS hypoxia increased FVC from baseline (21 ± 3%; P < 0.05). Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min to inhibit NOS during continuous SS hypoxia reduced FVC by -33 ± 3% (P < 0.05). In Trial 2 with continuous NOS inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (20 ± 3%), and infusion of ketorolac for 5 min to inhibit COX during continuous SS hypoxia reduced FVC by -15 ± 3% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). In group 2 (n = 10), the order of NOS and COX inhibition was reversed. In trial 1, five minutes of SS hypoxia increased FVC from baseline (by 24 ± 5%; P < 0.05), and infusion of ketorolac during SS hypoxia had minimal impact on FVC (-4 ± 3%; NS). In Trial 2 with continuous COX inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (27 ± 4%), and infusion of L-NAME during continuous SS hypoxia reduced FVC by -36 ± 7% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). Our collective findings indicate that (1) neither NO nor PGs are obligatory to observe the normal local vasodilatory response from rest to SS hypoxia; (2) NO regulates vascular tone during hypoxia independent of the COX pathway, whereas PGs only regulate vascular tone during hypoxia when NOS is inhibited; and (3) combined inhibition of NO and PGs abolishes local hypoxic vasodilatation (from rest to SS hypoxia) in the forearm circulation of healthy humans during systemic hypoxia.
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Effects of acupuncture at 7-9 am and 3-5 pm on plasma thromboxane and prostaglandin in patients with ischemic cerebrovascular disease.
Zhang, FH
Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan. 2010;(1):9-12
Abstract
OBJECTIVE To observe the effects of acupuncture at different times on plasma thromboxane (TXB2) and prostaglandin 6-Keto-PGF1a (6-K-P) in patients with ischemic cerebrovascular disease. METHODS Totally 90 patients were randomly divided into a group acupunctured at 7-9 am, a group acupunctured at 3-5 pm and a drug control group, with 30 cases in each group. The contents of plasma TXB2 and 6-K-P from venous blood before treatment were compared with those 15 days after treatment. RESULTS The plasma TXB2 levels of the two acupuncture groups were obviously lower than those before treatment (P < 0.05, P < 0.01), but the 6-K-P levels of both the acupuncture groups were remarkably higher than those before treatment (P < 0.05, P < 0.01). and the TXB2 level in the 3-5 pm acupuncture group was obviously lower than that in the 7-9 am acupuncture group (P < 0.05), and the 6-K-P level of the former was obviously higher than that of the latter (P < 0.05). CONCLUSION Acupuncture can promote functional recovery in patients with ischemic cerebrovascular disease and enhance their survival quality.
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Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels.
Lauridsen, TG, Vase, H, Starklint, J, Graffe, CC, Bech, JN, Nielsen, S, Pedersen, EB
BMC nephrology. 2010;:28
Abstract
BACKGROUND Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. METHODS The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. RESULTS Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. CONCLUSION During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system TRIAL REGISTRATION Clinical Trials Identifier: NCT00281762.
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Differential suppression of menstrual fluid prostaglandin F2a, prostaglandin E2, 6-keto prostaglandin F1a and thromboxane B2 by suprofen in women with primary dysmenorrhea.
Dawood, MY, Khan-Dawood, FS
Prostaglandins & other lipid mediators. 2007;(1-2):146-53
Abstract
Eleven women with primary dysmenorrhea completed a randomized, double-blind, placebo-controlled, three-way cross-over study comparing 200 and 400mg suprofen. Menstrual fluid volume did not change. Mean+/-S.E.M. menstrual fluid PGF2a was significantly suppressed from 18.9+/-1.9 microg (placebo) to 10.9+/-1.7 and 9.3+/-2.1 microg with 200 and 400 mg suprofen, respectively (p=<0.005). PGE2 dropped from 7.8+/-0.9 to 4.6+/-0.8 and 4.6+/-1.1 microg (p=<0.05) and TxB2 from 17.5+/-4.3 to 7.5+/-2.9 and 3.6+/-1.3 microg (p=<0.01), respectively. 6-Keto PGF1a was significantly suppressed (2.7+/-0.4 to 1.9+/-0.5 microg, p=<0.025) with only 400 mg suprofen. Six subjects rated placebo poor and five fair to very good. In contrast, nine rated suprofen excellent to fair while two rated poor. Thus, suprofen was clinically effective but the differential suppression of prostanoids favors 200mg which spares 6-keto PGF1a.