Effects of Dynamic Exercise on Plasma Arachidonic Acid Epoxides and Diols in Human Volunteers

2011 ◽  
Vol 21 (6) ◽  
pp. 471-479 ◽  
Author(s):  
Rose M. Giordano ◽  
John W. Newman ◽  
Theresa L. Pedersen ◽  
Marisa I. Ramos ◽  
Charles L. Stebbins

Metabolites of the cytochrome P450 (CYP) pathway may contribute to vasodilation of the vasculature. However, it is not known whether exercise affects their circulating concentrations. The authors determined effects of exercise intensity and duration on plasma concentrations of epoxy and dihydroxy metabolites of arachidonic acid. Their goal was to delineate the threshold workload, optimal workload, and duration required to produce increases in plasma concentrations of these vasoactive substances. Healthy volunteers (N = 14) performed maximal exercise testing on a bicycle ergometer during Visit 1. On separate days, subjects cycled for 20 min at 30%, 60%, and 80% of their maximal exercise intensity. The last day consisted of 40 min of exercise at 60% of maximal exercise intensity. Venous blood was obtained before, during, and after exercise for analysis. Compared with rest, increases were observed during the 80% workload at 20 min postexercise —14,15-DHET (0.77 ± 0.21 vs. 0.93 ± 0.27 nM)—and at 2 min postexercise: 11,12-DHET (0.64 ± 0.22 vs. 0.71 ± 0.24 nM; p < .05). Also compared with rest, 40-min values during the 60% workload were 14,15-DHET 0.79 ± 0.22 vs. 0.91 ± 0.31 nM and at 2 min post 14,15 EET 0.12 ± 0.06 vs. 0.21 ± 0.16 nM (p < .05). Results suggest the CYP metabolites (i.e., DHETs) are released during short-term high-intensity and long-term moderateintensity exercise.

1997 ◽  
Vol 273 (6) ◽  
pp. L1132-L1140 ◽  
Author(s):  
Linhua Pang ◽  
Alan J. Knox

Prostanoids may be involved in bradykinin (BK)-induced bronchoconstriction in asthma. We investigated whether cyclooxygenase (COX)-2 induction was involved in prostaglandin (PG) E2 release by BK in cultured human airway smooth muscle (ASM) cells and analyzed the BK receptor subtypes responsible. BK stimulated PGE2release, COX activity, and COX-2 induction in a concentration- and time-dependent manner. It also time dependently enhanced arachidonic acid release. In short-term (15-min) experiments, BK stimulated PGE2 generation but did not increase COX activity or induce COX-2. In long-term (4-h) experiments, BK enhanced PGE2 release and COX activity and induced COX-2. The long-term responses were inhibited by the protein synthesis inhibitors cycloheximide and actinomycin D and the steroid dexamethasone. The effects of BK were mimicked by the B2-receptor agonist [Tyr(Me)8]BK, whereas the B1 agonist des-Arg9-BK was weakly effective at high concentrations. The B2antagonist HOE-140 potently inhibited all the effects, but the B1 antagonist des-Arg9,(Leu8)-BK was inactive. This study is the first to demonstrate that BK can induce COX-2. Conversion of increased arachidonic acid release to PGE2 by COX-1 is mainly involved in the short-term effect, whereas B2 receptor-related COX-2 induction is important in the long-term PGE2 release.


1990 ◽  
Vol 61 (3-4) ◽  
pp. 294-301 ◽  
Author(s):  
Jon Linderman ◽  
Thomas D. Fahey ◽  
Gregory Lauten ◽  
Alan S. Brooker ◽  
Doug Bird ◽  
...  

2018 ◽  
Vol 5 (2) ◽  
pp. 97 ◽  
Author(s):  
Mark Wallace, MD ◽  
Dwight E. Moulin, MD ◽  
Richard L. Rauck, MD ◽  
Sarita Khanna, PhD ◽  
Iulia Cristina Tudor, PhD ◽  
...  

Objective: To assess the safety and efficacy of long-term repeated dosing of OROS® hydromorphone in chronic pain patients.Design: This multicenter, open-label extension trial enrolled patients from three short-term OROS® hydromorphone trials.Setting: Fifty-six centers in the United States and Canada.Patients: Adults with chronic cancer pain or chronic nonmalignant pain who were receiving stable doses of OROS® hydromorphone (≥8 mg/day). Three hundred and eighty-eight patients were enrolled, 106 patients completed at least 12 months of therapy.Interventions: OROS® hydromorphone (individualized doses) was administered once daily.Main outcome measures: Safety and efficacy (Brief Pain Inventory and patient and investigator global evaluations) were assessed at monthly visits.Results: The median duration of extended OROS® hydromorphone therapy was 274 days. The median daily dose of study medication was 32.0 mg at extension-study baseline, 40.0 mg at month 3, and 48.0 mg at months 6, 9, and 12, respectively. The most frequently reported adverse events were nausea (n = 93, 24.0 percent) and constipation (n = 75, 19.3 percent). The analgesic effects of OROS® hydromorphone, assessed using the Brief Pain Inventory, were maintained throughout the extension. At 12 months, 72.4 percent of patients and 75.9 percent of investigators rated overall treatment as good, very good, or excellent.Conclusions: Once-daily OROS® hydromorphone is an osmotically driven, controlled-release preparation that may be particularly well suited to long-term use, because it provides consistent plasma concentrations and sustained around-the-clock analgesia. In this study, the benefits of OROS® hydromorphone attained in short-term studies were maintained in the long-term when daily administration was continued.


1998 ◽  
Vol 274 (1) ◽  
pp. E102-E107 ◽  
Author(s):  
A. Bonen ◽  
K. J. A. McCullagh ◽  
C. T. Putman ◽  
E. Hultman ◽  
N. L. Jones ◽  
...  

We examined the effects of increasing a known lactate transporter protein, monocarboxylate transporter 1 (MCT1), on lactate extrusion from human skeletal muscle during exercise. Before and after short-term bicycle ergometry training [2 h/day, 7 days at 65% maximal oxygen consumption (V˙o 2 max)], subjects ( n = 7) completed a continuous bicycle ergometer ride at 30%V˙o 2 max (15 min), 60%V˙o 2 max (15 min), and 75% V˙o 2 max (15 min). Muscle biopsy samples (vastus lateralis) and arterial and femoral venous blood samples were obtained before exercise and at the end of each workload. After 7 days of training the MCT1 content in muscle was increased (+18%; P < 0.05). The concentrations of both muscle lactate and femoral venous lactate were reduced during exercise ( P < 0.05) that was performed after training. High correlations were observed between muscle lactate and venous lactate before training ( r = 0.92, P < 0.05) and after training ( r = 0.85, P < 0.05), but the slopes of the regression lines between these variables differed markedly. Before training, the slope was 0.12 ± 0.01 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1, and this was increased by 33% after training to 0.18 ± 0.02 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1. This indicated that after training the femoral venous lactate concentrations were increased for a given amount of muscle lactate. These results suggest that lactate extrusion from exercising muscles is increased after training, and this may be associated with the increase in skeletal muscle MCT1.


1978 ◽  
Vol 76 (1) ◽  
pp. 1-10
Author(s):  
RONALD M. JONES ◽  
STANLEY S. HILLMAN

(1) Batrachoseps attenuatus and B. major were successfully acclimated to 600 m-osmol NaCl and 400 m-osmol sucrose solutions. (2) Accumulation of sodium and an increased rate of synthesis of urea provide substantial increases in plasma concentrations of these solutes. Sodium concentrations in excess of 230 mM and urea concentrations in excess of 200 mM indicate that these are the two major solutes (plus anions) responsible for elevation of osmotic concentration in Batrachoseps. (3) Batrachoseps exhibits a water balance response upon dehydration (greater than twofold increase in cutaneous uptake, 50% reduction in urine production). Urine production, estimated from bladder contents, was significantly reduced in salamanders acclimated to sucrose solutions compared to animals acclimated to tap water or saline of equivalent osmotic concentration. (4) Plasma urea concentration was equivalent to urine urea concentration when Batrachoseps was kept in tap water and during short term saline acclimation. After long term saline acclimation, urine urea concentration was one-fourth the plasma urea concentration.


2009 ◽  
Vol 34 (4) ◽  
pp. 616-624 ◽  
Author(s):  
Chin Leong Lim ◽  
David Pyne ◽  
Peggy Horn ◽  
Amelia Kalz ◽  
Philo Saunders ◽  
...  

The effects of increased training (IT) load on plasma concentrations of lipopolysaccharides (LPS), proinflammatory cytokines, and anti-LPS antibodies during exercise in the heat were investigated in 18 male runners, who performed 14 days of normal training (NT) or 14 days of 20% IT load in 2 equal groups. Before (trial 1) and after (trial 2) the training intervention, all subjects ran at 70% maximum oxygen uptake on a treadmill under hot (35 °C) and humid (∼40%) conditions, until core temperature reached 39.5 °C or volitional exhaustion. Venous blood samples were drawn before, after, and 1.5 h after exercise. Plasma LPS concentration after exercise increased by 71% (trial 1, p < 0.05) and 21% (trial 2) in the NT group and by 92% (trial 1, p < 0.01) and 199% (trial 2, p < 0.01) in the IT group. Postintervention plasma LPS concentration was 35% lower before exercise (p < 0.05) and 47% lower during recovery (p < 0.01) in the IT than in the NT group. Anti-LPS IgM concentration during recovery was 35% lower in the IT than in the NT group (p < 0.05). Plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations after exercise (IL-6, 3−7 times, p < 0.01, and TNF-α, 33%, p < 0.01) and during recovery (IL-6, 2−4 times, p < 0.05, and TNF-α, 30%, p < 0.01) were higher than at rest within each group. These data suggest that a short-term tolerable increase in training load may protect against developing endotoxemia during exercise in the heat.


1982 ◽  
Vol 53 (6) ◽  
pp. 1529-1539 ◽  
Author(s):  
J. E. Wilkerson ◽  
S. M. Horvath ◽  
B. Gutin ◽  
S. Molnar ◽  
F. J. Diaz

Five healthy males volunteered to exercise for 20 min on a motor-driven treadmill at five submaximal intensities (30, 45, 60, 75, and 90% of VO2 max). Peripheral venous blood samples were drawn from an indwelling catheter prior to and at 9, 14, and 19 min of each exercise bout. Blood samples were assayed for whole-blood hemoglobin, total plasma protein concentrations, and hematocrit, with plasma water concentration calculated from these values. The plasma concentration of the electrolytes sodium (Na+), potassium (K+), total calcium (Catot), ionized calcium (Ca2+), chloride (Cl-), and inorganic phosphorus (Pi) were also determined. With plasma and blood volumes the total plasma contents of each of the measured constituents and the concentration of each electrolyte per liter of water were calculated. Statistically significant linear increases in plasma concentrations of Na+, K+, and Cl- relative to exercise intensity were observed, with linear decreases in plasma contents of Na+ and Cl- and linear increases in K+ content. Plasma Pi concentration decreased with a Pi increased content, with plasma Catot concentration elevated at the highest two work loads. Plasma Catot content increased linearly with exercise intensity and duration. Plasma water concentration and content decreased with exercise intensity, resulting in no change in electrolyte concentration per liter of water except at the highest two exercise intensities. These data suggest that extrapolation from plasma electrolyte concentration to muscle concentration and/or content is not supported. Changes in plasma volume and plasma water must be considered when postulating a role for electrolytes in the physiological responses of the human to exercise.


2018 ◽  
Vol 39 (11) ◽  
pp. 867-874 ◽  
Author(s):  
Emmanuelle Rochette ◽  
Etienne Merlin ◽  
Christophe Hourdé ◽  
Bertrand Evrard ◽  
Bruno Peraira ◽  
...  

AbstractThe aim of this study was to measure the impact, at 24 h post-exercise, of a single exercise bout on plasma inflammatory markers such as calprotectin, IL-6, sIL-6 R, sgp130 and the hypothalamic-pituitary-adrenal (HPA) axis in children with juvenile idiopathic arthritis (JIA).Twelve children with JIA attended the laboratory on three consecutive days (control day, exercise day and 24 h post-exercise), including a 20-min exercise bout on a cycle-ergometer at 70% of max. HR at 8:30 a.m. on day 2. Plasma concentrations of calprotectin, IL-6, sIL-6 R, sgp130, cortisol, ACTH and DHEA were measured on venous blood samples taken every day.at rest and at 8:30, 8:50, 9:30, 10:30 a.m. and 12:00, 3:00, 5:30 p.m.A single exercise bout increased plasma calprotectin 1.7-fold (p<0.001) but did not increase IL-6 and soluble IL-6 receptors in short-term post-exercise recovery. However, at 24 h post-exercise, calprotectin, IL-6 and its receptors had decreased compared to control-day levels. There was a transient 2-fold increase in post-exercise self-evaluated pain (p=0.03) that disappeared in the evening without repercussions the following day.Physical activity in children with JIA results in a slight transient systemic inflammation but seems to be followed by counter-regulation at 24 h post-exercise with a decrease in proinflammatory markers.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Wenjun Deng ◽  
David McMullin ◽  
Thomas Wickham ◽  
Kathleen Feeney ◽  
Ignacio Inglessis ◽  
...  

Background: PFO allows venous clots and vasoactive circulatory factors to bypass pulmonary filtration and remain in circulation. Serotonin (5-HT) has procoagulant and oxidative roles in both cardiovascular and neurovascular injury. We previously identified an immediate reduction of 5-HT in left atrial blood post PFO closure. To understand the long-term effect of PFO closure, we report the changes of 5-HT in peripheral venous blood in 1-year follow-up. Method: 97 PFO-related stroke patients were recruited in accordance with IRB. Venous blood was collected at baseline (BL) and 1 year follow-up (FU) post treatment (PFO closure or medical therapy). Plasma 5-HT was quantified by mass spectrometry. Patients with serotonin modifying medications (e.g. SSRIs) or conditions (e.g. anxiety/depression) were excluded. Result: 5-HT concentration in peripheral venous blood was significantly reduced by 27.27% (BL: 7.57 ± 8.04 μmol/l; FU: 5.51 ± 5.72 μmol/l; p = 0.0034) in 61 patients receiving PFO closure (Fig 1A). In the 37 PFO patients treated with medical therapy alone, no changes were observed (5-HT: BL: 5.79 ± 7.15 μmol/l; FU: 6.25 ± 6.68 μmol/l; p = 0.4050) (Fig 1B). This decrease in serotonin was independently associated with PFO closure after adjusting for age, gender, medical history and medication status in a multivariate regression (Fig 1C). Conclusion: We found that PFO closure independently reduced 5-HT level in peripheral venous blood. These results support the hypothesis that PFO associated right-to-left interatrial shunting may foster higher levels of procoagulant and vasoactive substances in circulation. We have previously found PFO closure to decrease prothrombotic markers immediately post closure; this effect is now shown also to be sustained in long term follow-up up to 1 year. Further studies are ongoing on the clinical outcome of these PFO related stroke patients with respect to their prothrombotic circulatory profiles.


2021 ◽  
Author(s):  
Zijun Wang ◽  
Ying Cao ◽  
Jinhua Su ◽  
Hong Gao ◽  
Meiwu Zhou ◽  
...  

Abstract Background: The purpose of our study was to evaluate the effect of 6% desflurane on short-term olfactory memory after laparoscopic surgery, and to investigate whether plasma concentrations of plasma S-100β protein, neuron specific enolase (NSE) and melatonin correlate with it.Methods: We collected medical data of patients who underwent laparoscopic surgery in the Second People's Hospital of Guiyang during May 2018 - February 2020. A total of 40 patients, who were aged 18-60 years old with American Society of Anesthesiologists (ASA) physical status I-II, were enrolled in the study. During the operation, the patients inhaled 6% desflurane to maintain the anesthesia. Patients were brought to the recovery room 45 minutes prior to the surgery (T0). And the patients were sent to the post-anesthesia care unit (PACU) after the surgery, if their Aldrete score was ≥ 9 points (T1), the CCCRC test was repeated to re-assess their olfactory memory. Venous blood samples (3 mL) were collected at T0 and T1, and the plasma was centrifuged at 3,000 rpm and then stored in a refrigerator at -20°C. Plasma S-100β protein, NSE, and melatonin levels were determined using ELISA.Results: There was no statistically significant difference in the odor identification score between T0 and T1 (P > 0.05). As compared with T0, the plasma concentrations of S-100β protein and NSE declined at T1. However, these differences were not statistically significant (P > 0.05). There were also no statistically significant changes in melatonin levels between T0 and T1 (P > 0.05).Conclusions: This study found that undergoing general anesthesia with the inhaled anesthetic desflurane did not affect the short-term olfactory memory of patients undergoing laparoscopic surgery. This may be explained by the proposition that desflurane maintains plasma S-100β protein, NSE, and melatonin levels.Trial registration: Chinese Clinical Trial Registry (URL: http:// www.chictr.org.cn. Registry number: ChiCTR2100049441 ). Date of Registration: 2 August 2021.


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