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Inger Jansenolesen - One of the best experts on this subject based on the ideXlab platform.
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infusion of low dose Glyceryl Trinitrate has no consistent effect on burrowing behavior running wheel activity and light sensitivity in female rats
Journal of Pharmacological and Toxicological Methods, 2016Co-Authors: Sarah L Christensen, Dorte Bratbo Sørensen, Steffen E. Petersen, Inger JansenolesenAbstract:Abstract Introduction Glyceryl Trinitrate induces headache during infusion to man and migraine patients develop an additional migraine attack a few hours after the infusion. Recently, we have moved this model into rat with the intention of developing an animal model predictive of migraine therapy. In the current paper we have studied the effect of Glyceryl Trinitrate infusion on three different rat behaviors. Methods The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of Glyceryl Trinitrate on these behaviors in female rats was observed. Results Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None of the three behavioral tests were altered by Glyceryl Trinitrate infusion. In the light–dark box, some batches of rats showed light sensitivity after treatment with Glyceryl Trinitrate but it could not be repeated in other batches of rats. Discussion We have investigated the stability towards repeated testing and the effect of i.v. Glyceryl Trinitrate infusion to awake rats in three behavioral assays. Of the assays evaluated, only light sensitivity was capable of detecting changes after Glyceryl Trinitrate infusion but, this was not repeatable. Thus, the infusion of a low dose Glyceryl Trinitrate to concious rats together with the chosen behavioral tests is not a robust setup for studying immediate GTN induced headache behavior in rats.
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mechanisms of Glyceryl Trinitrate provoked mast cell degranulation
Cephalalgia, 2015Co-Authors: Sara Hougaard Pedersen, Dipak Vasantrao Amrutkar, Roshni Ramachandran, Steffen E. Petersen, Inger JansenolesenAbstract:BackgroundMigraine patients develop attacks several hours after intravenous infusion of Glyceryl Trinitrate. Due to the short half-life of nitric oxide, this delayed migraine cannot be caused by a direct action of nitric oxide derived from Glyceryl Trinitrate. The involvement of meningeal inflammation and dural mast cell degranulation is supported by the effectiveness of prednisolone on Glyceryl Trinitrate-induced delayed headache.MethodsUsing a newly developed rat model mimicking the human Glyceryl Trinitrate headache model, we have investigated the occurrence of dural mast cell degranulation after a clinically relevant dose of Glyceryl Trinitrate.ResultsA 6-fold increase in degranulation was observed starting at 2 hours after Glyceryl Trinitrate infusion. Interestingly, pre-treatment with the effective anti-migraine substances L-nitro-arginine methyl ester and sumatriptan prevented Glyceryl Trinitrate-induced mast cell degranulation whereas the calcitonin gene-related peptide-receptor antagonist olcegep...
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ehmti 0234 Glyceryl Trinitrate provoked mast cell degranulation is secondary to the release of nitric oxide in vivo
Journal of Headache and Pain, 2014Co-Authors: Hougaard S Pedersen, Dipak Vasantrao Amrutkar, Roshni Ramachandran, Steffen E. Petersen, Jes Olesen, Inger JansenolesenAbstract:Infusion of the nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), provokes a migraine-like attack in migraineurs and cFos up-regulation in rat trigeminal nucleus caudalis. We studied the level of dura mast cell degranulation after infusion of GTN in awake, freely moving rats and hypothesized that the degranulation is secondary to NO.
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a naturalistic Glyceryl Trinitrate infusion migraine model in the rat
Cephalalgia, 2012Co-Authors: Roshni Ramachandran, Inger Jansenolesen, Jes Olesen, Deepak Kumar Bhatt, Kenneth Beri Ploug, Anders Hayschmidt, Saurabh GuptaAbstract:Background: and aim Glyceryl Trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine is not certain. Anaesthesia and low blood pressure caused by high GTN doses both can affect the expression of nociceptive marker c-fos. Therefore, our aim was to simulate the human GTN migraine model in awake rats using a clinically relevant dose.Methods: Awake rats were infused with GTN (4 µg/kg/min, for 20 min, i.v.), a dose just 8 times higher than in humans. mRNA and protein expression for c-fos were analysed in the trigeminal vascular system at various time points using RT-PCR and immunohistochemistry, respectively.Results: A significant upregulation of c-fos mRNA was observed in the trigeminal nucleus caudalis at 30 min and 2 h that was followed by an upregulation of Fos protein in the ...
Jason P. Appleton - One of the best experts on this subject based on the ideXlab platform.
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prehospital transdermal Glyceryl Trinitrate for ultra acute intracerebral hemorrhage data from the right 2 trial
Stroke, 2019Co-Authors: Philip M.w. Bath, Lisa J Woodhouse, Mark Dixon, Timothy J England, Eivind Berge, Craig S Anderson, L A Cala, Jason P. Appleton, Kailash Krishnan, Peter J GodolphinAbstract:Background and Purpose— Pilot trials suggest that Glyceryl Trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, param...
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baseline characteristics of the 1149 patients recruited into the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 randomized controlled trial
International Journal of Stroke, 2019Co-Authors: Lisa J Woodhouse, Mark Dixon, Polly Scutt, Jason P. Appleton, Philip M.w. Bath, Nikola Sprigg, Joanna M WardlawAbstract:BackgroundHigh blood pressure is common in acute stroke and associated with a worse functional outcome. Glyceryl Trinitrate, a nitric oxide donor, lowers blood pressure in acute stroke and may impr...
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ambulance delivered transdermal Glyceryl Trinitrate versus sham for ultra acute stroke rationale design and protocol for the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 trial isrctn26986053
International Journal of Stroke, 2019Co-Authors: Jason P. Appleton, Mark Dixon, Timothy J England, Polly Scutt, Harriet Howard, Lee Haywood, Diane Havard, Nikola Sprigg, Trish Hepburn, Lisa J WoodhouseAbstract:RationaleVascular nitric oxide levels are low in acute stroke and donors such as Glyceryl Trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action inc...
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ambulance delivered transdermal Glyceryl Trinitrate versus sham for ultra acute stroke rationale design and protocol for the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 trial isrctn26986053
International Journal of Stroke, 2019Co-Authors: Jason P. Appleton, Mark Dixon, Timothy J England, Polly Scutt, Harriet Howard, Lee Haywood, Diane Havard, Nikola Sprigg, Trish Hepburn, Lisa J WoodhouseAbstract:Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as Glyceryl Trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim: To test the safety and efficacy of four days of transdermal Glyceryl Trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates: The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (Glyceryl Trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design: The Rapid Intervention with Glyceryl Trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (4 h of onset) FAST-positive presumed stroke and systolic blood pressure 120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes: The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion: RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status: Trial is ongoing. Funding: British Heart Foundation. Registration: ISRCTN26986053.
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effect of Glyceryl Trinitrate on hemodynamics in acute stroke
Stroke, 2019Co-Authors: Lisa J Woodhouse, Eivind Berge, Jason P. Appleton, Daniel Bereczki, Hanne Christensen, Ronan Collins, John Gommans, George Ntaios, Serefnur OzturkAbstract:Background and Purpose— Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of Glyceryl Trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods— Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results— Increased baseline BP (diastolic, variability), heart rate, ...
Lisa J Woodhouse - One of the best experts on this subject based on the ideXlab platform.
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prehospital transdermal Glyceryl Trinitrate for ultra acute intracerebral hemorrhage data from the right 2 trial
Stroke, 2019Co-Authors: Philip M.w. Bath, Lisa J Woodhouse, Mark Dixon, Timothy J England, Eivind Berge, Craig S Anderson, L A Cala, Jason P. Appleton, Kailash Krishnan, Peter J GodolphinAbstract:Background and Purpose— Pilot trials suggest that Glyceryl Trinitrate (GTN; nitroglycerin) may improve outcome when administered early after stroke onset. Methods— We undertook a multicentre, param...
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baseline characteristics of the 1149 patients recruited into the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 randomized controlled trial
International Journal of Stroke, 2019Co-Authors: Lisa J Woodhouse, Mark Dixon, Polly Scutt, Jason P. Appleton, Philip M.w. Bath, Nikola Sprigg, Joanna M WardlawAbstract:BackgroundHigh blood pressure is common in acute stroke and associated with a worse functional outcome. Glyceryl Trinitrate, a nitric oxide donor, lowers blood pressure in acute stroke and may impr...
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ambulance delivered transdermal Glyceryl Trinitrate versus sham for ultra acute stroke rationale design and protocol for the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 trial isrctn26986053
International Journal of Stroke, 2019Co-Authors: Jason P. Appleton, Mark Dixon, Timothy J England, Polly Scutt, Harriet Howard, Lee Haywood, Diane Havard, Nikola Sprigg, Trish Hepburn, Lisa J WoodhouseAbstract:RationaleVascular nitric oxide levels are low in acute stroke and donors such as Glyceryl Trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action inc...
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ambulance delivered transdermal Glyceryl Trinitrate versus sham for ultra acute stroke rationale design and protocol for the rapid intervention with Glyceryl Trinitrate in hypertensive stroke trial 2 right 2 trial isrctn26986053
International Journal of Stroke, 2019Co-Authors: Jason P. Appleton, Mark Dixon, Timothy J England, Polly Scutt, Harriet Howard, Lee Haywood, Diane Havard, Nikola Sprigg, Trish Hepburn, Lisa J WoodhouseAbstract:Rationale: Vascular nitric oxide levels are low in acute stroke and donors such as Glyceryl Trinitrate have shown promise when administered very early after stroke. Potential mechanisms of action include augmentation of cerebral reperfusion, thrombolysis and thrombectomy, lowering blood pressure, and cytoprotection. Aim: To test the safety and efficacy of four days of transdermal Glyceryl Trinitrate (5 mg/day) versus sham in patients with ultra-acute presumed stroke who are recruited by paramedics prior to hospital presentation. Sample size estimates: The sample size of 850 patients will allow a shift in the modified Rankin Scale with odds ratio 0.70 (Glyceryl Trinitrate versus sham, ordinal logistic regression) to be detected with 90% power at 5% significance (two-sided). Design: The Rapid Intervention with Glyceryl Trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is a multicentre UK prospective randomized sham-controlled outcome-blinded parallel-group trial in 850 patients with ultra-acute (4 h of onset) FAST-positive presumed stroke and systolic blood pressure 120 mmHg who present to the ambulance service following a 999 emergency call. Data collection is performed via a secure internet site with real-time data validation. Study outcomes: The primary outcome is the modified Rankin Scale measured centrally by telephone at 90 days and masked to treatment. Secondary outcomes include: blood pressure, impairment, recurrence, dysphagia, neuroimaging markers of the acute lesion including vessel patency, discharge disposition, length of stay, death, cognition, quality of life, and mood. Neuroimaging and serious adverse events are adjudicated blinded to treatment. Discussion: RIGHT-2 has recruited more than 500 participants from seven UK ambulance services. Status: Trial is ongoing. Funding: British Heart Foundation. Registration: ISRCTN26986053.
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effect of Glyceryl Trinitrate on hemodynamics in acute stroke
Stroke, 2019Co-Authors: Lisa J Woodhouse, Eivind Berge, Jason P. Appleton, Daniel Bereczki, Hanne Christensen, Ronan Collins, John Gommans, George Ntaios, Serefnur OzturkAbstract:Background and Purpose— Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of Glyceryl Trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods— Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results— Increased baseline BP (diastolic, variability), heart rate, ...
George A. C. Murrell - One of the best experts on this subject based on the ideXlab platform.
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randomised double blind placebo controlled clinical trial of a new topical Glyceryl Trinitrate patch for chronic lateral epicondylosis
British Journal of Sports Medicine, 2009Co-Authors: Justin A. Paoloni, George A. C. Murrell, Ronald BurchAbstract:Objective: This study aimed to determine whether a new Glyceryl Trinitrate patch preparation is effective in treating chronic lateral epicondylosis. Design: Randomised double-blind controlled clinical trial. Setting: Private practice patients: 154 adult patients with chronic lateral epicondylosis were recruited, with 136 patients completing the trial. Interventions: 8 weeks of Glyceryl Trinitrate patch application (dosages of 72 mg/24 h, 1.44 mg/24 h, and 3.6 mg/24 h), or placebo patch application. Main outcome measures: Subjective global assessment of change in elbow symptoms, patient-rated tennis elbow evaluation, visual analogue pain at rest, visual analogue pain with activity, visual analogue pain intensity, grip strength, and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System. Results: At 8 weeks there was a significant decrease in elbow pain with activity in the Glyceryl Trinitrate 0.72 mg/24 h group compared with placebo (p = 0.04). There were no other significant differences. Conclusions: Continuous 1.25 mg/24 h topical Glyceryl Trinitrate treatment, when combined with daily exercise rehabilitation, has previously demonstrated efficacy in treating chronic lateral epicondylosis. There was significantly decreased elbow pain with activity at 8 weeks in the Glyceryl Trinitrate 0.72 mg/24 h group (p = 0.04). This short-term dose-ranging study did not demonstrate a treatment effect of a new topical Glyceryl Trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h, which conflicts with previous studies on topical Glyceryl Trinitrate treatment. Trial registration number: NCT00447928.
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three year followup study of topical Glyceryl Trinitrate treatment of chronic noninsertional achilles tendinopathy
Foot & Ankle International, 2007Co-Authors: Justin A. Paoloni, George A. C. MurrellAbstract:Background: Topical Glyceryl Trinitrate treatment has demonstrated short-term efficacy in chronic noninsertional Achilles tendinopathy. No long-term followup is reported. We aimed to assess if the ...
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topical Glyceryl Trinitrate application in the treatment of chronic supraspinatus tendinopathy a randomized double blinded placebo controlled clinical trial
American Journal of Sports Medicine, 2005Co-Authors: Justin A. Paoloni, Janis Nelson, Richard Appleyard, George A. C. MurrellAbstract:Background: Topical Glyceryl Trinitrate therapy has previously demonstrated short-term pain reduction in patients with supraspinatus tendinopathy.Hypothesis: Topical Glyceryl Trinitrate improves outcome measures in patients with supraspinatus tendinopathy.Study Design: Randomized controlled clinical trial; Level of evidence, 1.Methods: Fifty-three patients (57 shoulders) were recruited, and the authors completed a prospective, randomized, double-blinded, placebo-controlled clinical trial of continuous topical Glyceryl Trinitrate treatment (1.25 mg/24-h Glyceryl Trinitrate).Results: The Glyceryl Trinitrate group had significantly reduced shoulder pain with activity, at night, and at rest at week 24 (P = .03); reduced internal rotation impingement at week 24 (P = .02); increased range of motion in abduction and internal rotation at week 24 (P = .04); and increased force at weeks 12 and 24 with supraspinatus muscle testing (P = .001), external rotation (P = .04), internal rotation (P = .01), adduction (P = ....
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topical Glyceryl Trinitrate treatment of chronic noninsertional achilles tendinopathy a randomized double blind placebo controlled trial
Journal of Bone and Joint Surgery American Volume, 2004Co-Authors: Justin A. Paoloni, Janis Nelson, Richard Appleyard, George A. C. MurrellAbstract:Background: Noninsertional Achilles tendinopathy is a degenerative overuse disorder. No method has been universally successful in treating this condition. Topically applied nitric oxide has been shown, in animal models, to be effective for the treatment of fractures and cutaneous wounds through mechanisms that may include stimulation of collagen synthesis in fibroblasts. The goal of the present study was to determine if topical Glyceryl Trinitrate improves clinical outcome measures in patients with Achilles tendinopathy. Methods: A prospective, randomized, double-blind, placebo-controlled trial involving a total of sixty-five patients (eighty-four Achilles tendons) was performed to compare continuous application of topical Glyceryl Trinitrate (at a dosage of 1.25 mg per twenty-four hours) with rehabilitation alone for the treatment of noninsertional Achilles tendinopathy. Results: Compared with the control group, the Glyceryl Trinitrate group showed reduced pain with activity at twelve weeks (p = 0.02) and twenty-four weeks (p = 0.03), reduced night pain at twelve weeks (p = 0.04), reduced tenderness at twelve weeks (p = 0.02), decreased pain scores after the hop test at twenty-four weeks (p = 0.005), and increased ankle plantar flexor mean total work compared with the baseline level at twenty-four weeks (p = 0.04). Twenty-eight (78%) of thirty-six tendons in the Glyceryl Trinitrate group were asymptomatic with activities of daily living at six months, compared with twenty (49%) of forty-one tendons in the placebo group (p = 0.001, chi-square analysis). The mean effect size for all outcome measures was 0.14. Conculsions: Topical Glyceryl Trinitrate significantly reduced pain with activity and at night, improved functional measures, and improved outcomes in patients with Achilles tendinopathy. Level of Evidence: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence.
Jes Olesen - One of the best experts on this subject based on the ideXlab platform.
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ehmti 0234 Glyceryl Trinitrate provoked mast cell degranulation is secondary to the release of nitric oxide in vivo
Journal of Headache and Pain, 2014Co-Authors: Hougaard S Pedersen, Dipak Vasantrao Amrutkar, Roshni Ramachandran, Steffen E. Petersen, Jes Olesen, Inger JansenolesenAbstract:Infusion of the nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), provokes a migraine-like attack in migraineurs and cFos up-regulation in rat trigeminal nucleus caudalis. We studied the level of dura mast cell degranulation after infusion of GTN in awake, freely moving rats and hypothesized that the degranulation is secondary to NO.
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a naturalistic Glyceryl Trinitrate infusion migraine model in the rat
Cephalalgia, 2012Co-Authors: Roshni Ramachandran, Inger Jansenolesen, Jes Olesen, Deepak Kumar Bhatt, Kenneth Beri Ploug, Anders Hayschmidt, Saurabh GuptaAbstract:Background: and aim Glyceryl Trinitrate (GTN) infusion is a reliable method to provoke migraine-like headaches in humans. Previous studies have simulated this human model in anaesthetized or in awake rodents using GTN doses 10,000 times higher than used in humans. The relevance of such toxicological doses to migraine is not certain. Anaesthesia and low blood pressure caused by high GTN doses both can affect the expression of nociceptive marker c-fos. Therefore, our aim was to simulate the human GTN migraine model in awake rats using a clinically relevant dose.Methods: Awake rats were infused with GTN (4 µg/kg/min, for 20 min, i.v.), a dose just 8 times higher than in humans. mRNA and protein expression for c-fos were analysed in the trigeminal vascular system at various time points using RT-PCR and immunohistochemistry, respectively.Results: A significant upregulation of c-fos mRNA was observed in the trigeminal nucleus caudalis at 30 min and 2 h that was followed by an upregulation of Fos protein in the ...
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cgrp receptor antagonist olcegepant bibn4096bs does not prevent Glyceryl Trinitrate induced migraine
Cephalalgia, 2010Co-Authors: J F Tvedskov, P Tfelthansen, K A Petersen, L T Jensen, Jes OlesenAbstract:There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor Glyceryl Trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypot...