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Sports Health 2015Patellar tendinopathy is a common condition. There are a wide variety of treatment options available, the majority of which are nonoperative. No consensus exists on the... (Review)
Review
CONTEXT
Patellar tendinopathy is a common condition. There are a wide variety of treatment options available, the majority of which are nonoperative. No consensus exists on the optimal method of treatment.
EVIDENCE ACQUISITION
PubMed spanning 1962-2014.
STUDY DESIGN
Clinical review.
LEVEL OF EVIDENCE
Level 4.
RESULTS
The majority of cases resolve with nonoperative therapy: rest, physical therapy with eccentric exercises, cryotherapy, anti-inflammatories, corticosteroid injections, extracorporeal shockwave therapy, glyceryl trinitrate, platelet-rich plasma injections, and ultrasound-guided sclerosis. Refractory cases may require either open or arthroscopic debridement of the patellar tendon. Corticosteroid injections provide short-term pain relief but increase risk of tendon rupture. Anti-inflammatories and injectable agents have shown mixed results. Surgical treatment is effective in many refractory cases unresponsive to nonoperative modalities.
CONCLUSION
Physical therapy with an eccentric exercise program is the mainstay of treatment for patellar tendinopathy. Platelet-rich plasma has demonstrated mixed results; evidence-based recommendations on its efficacy cannot be made. In the event that nonoperative treatment fails, surgical intervention has produced good to excellent outcomes in the majority of patients.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Cryotherapy; Debridement; Exercise Therapy; High-Energy Shock Waves; Humans; Nitroglycerin; Patellar Ligament; Platelet-Rich Plasma; Sclerosing Solutions; Tendinopathy
PubMed: 26502416
DOI: 10.1177/1941738114568775 -
Circulation Journal : Official Journal... 2012Acute myocardial infarction (MI) and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin (glyceryl trinitrate [GTN]) remains a first-line... (Review)
Review
Acute myocardial infarction (MI) and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin (glyceryl trinitrate [GTN]) remains a first-line treatment for angina pectoris and acute MI. Nitroglycerin achieves its benefit by giving rise to nitric oxide (NO), which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of GTN results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is caused, at least in part, by inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts GTN to the vasodilator, NO. We recently found that in a MI model in animals, in addition to GTN's effect on the vasculature, sustained treatment negatively affected cardiomyocyte viability following ischemia, thus resulting in increased infarct size. Coadministration of Alda-1, an activator of ALDH2, with GTN improves metabolism of reactive aldehyde adducts and prevents the GTN-induced increase in cardiac dysfunction following MI. In this review, we describe the molecular mechanisms associated with the benefits and risks of GTN administration in MI.
Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Animals; Cell Survival; Drug Tolerance; Humans; Models, Animal; Myocardial Infarction; Myocytes, Cardiac; Nitroglycerin; Vasodilator Agents
PubMed: 22040938
DOI: 10.1253/circj.cj-11-1133 -
The Journal of Headache and Pain Sep 2018Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl... (Review)
Review
Although clinically distinguishable, migraine and cluster headache share prominent features such as unilateral pain, common pharmacological triggers such glyceryl trinitrate, histamine, calcitonin gene-related peptide (CGRP) and response to triptans and neuromodulation. Recent data also suggest efficacy of anti CGRP monoclonal antibodies in both migraine and cluster headache. While exact mechanisms behind both disorders remain to be fully understood, the trigeminovascular system represents one possible common pathophysiological pathway and network of both disorders. Here, we review past and current literature shedding light on similarities and differences in phenotype, heritability, pathophysiology, imaging findings and treatment options of migraine and cluster headache. A continued focus on their shared pathophysiological pathways may be important in paving future treatment avenues that could benefit both migraine and cluster headache patients.
Topics: Calcitonin Gene-Related Peptide; Cluster Headache; Deep Brain Stimulation; Humans; Implantable Neurostimulators; Migraine Disorders; Nitroglycerin; Tryptamines
PubMed: 30242519
DOI: 10.1186/s10194-018-0909-4 -
Therapeutic role of nitroglycerin against copper-nitrilotriacetate induced hepatic and renal damage.Human & Experimental Toxicology 2022Earlier we have shown that exposure to copper-nitrilotriacetate (Cu-NTA) manifests toxicity by generating oxidative stress and potent induction of proliferative reaction...
Earlier we have shown that exposure to copper-nitrilotriacetate (Cu-NTA) manifests toxicity by generating oxidative stress and potent induction of proliferative reaction in the liver and kidney. In the study, we look at the impact of nitroglycerin (GTN) administration on Cu-NTA-induced oxidative stress and hyperproliferative response in the liver and kidney. GTN administration intraperitoneally to male Wistar rats after Cu-NTA administration intraperitoneally caused substantial protection against Cu-NTA-induced tissue injury, oxidative stress and hyperproliferative response. Cu-NTA administration at a dose of 4.5 mg/kg body weight produces significant ( < .001) elevation in biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine (CREA) with a concomitant increase in microsomal lipid peroxidation. Along with these alterations, we discovered a substantial increment in [H]thymidine incorporation into hepatic and renal DNA synthesis ( < .001). Cu-NTA-induced tissue damage and lipid peroxidation in hepatic and renal tissues were inhibited by GTN treatment in a dose-dependent manner ( < .05-0.001). Furthermore, GTN can suppress the hyperproliferative response elicited by Cu-NTA by down-regulating the rate of [H]thymidine incorporation into hepatic and renal DNA ( < .01-0.001). Protective effect of GTN against Cu-NTA was also confirmed by histopathological changes in liver and kidney. This result suggests that GTN may serve as a scavenger for reactive oxygen species (ROS) and reduces toxic metabolites of Cu-NTA, thereby avoiding tissue injury and oxidative stress. Further, administration of NO inhibitor, NG-Nitroarginine methyl ester (L-NAME), exacerbated Cu-NTA induced oxidative tissue damage and cell proliferation. Overall, GTN reduces Cu-NTA-induced tissue damage, oxidative stress, and proliferative response in the rat liver and kidney, according to these findings. On the basis of the above results, present study suggests that GTN may be a potential therapeutic agent for restoration of oxidative damage and proliferation to liver and kidney.
Topics: Rats; Animals; Male; Nitroglycerin; Copper; Rats, Wistar; Kidney; Lipid Peroxidation; Nitrilotriacetic Acid; Oxidative Stress; Liver; Antioxidants; NG-Nitroarginine Methyl Ester; Thymidine; DNA; Ferric Compounds
PubMed: 36305384
DOI: 10.1177/09603271221131312 -
Cell Death & Disease May 2023Nitroglycerin (NTG) is a prodrug that has long been used in clinical practice for the treatment of angina pectoris. The biotransformation of NTG and subsequent release... (Review)
Review
Nitroglycerin (NTG) is a prodrug that has long been used in clinical practice for the treatment of angina pectoris. The biotransformation of NTG and subsequent release of nitric oxide (NO) is responsible for its vasodilatating property. Because of the remarkable ambivalence of NO in cancer disease, either protumorigenic or antitumorigenic (partly dependent on low or high concentrations), harnessing the therapeutic potential of NTG has gain interest to improve standard therapies in oncology. Cancer therapeutic resistance remains the greatest challenge to overcome in order to improve the management of cancer patients. As a NO releasing agent, NTG has been the subject of several preclinical and clinical studies used in combinatorial anticancer therapy. Here, we provide an overview of the use of NTG in cancer therapy in order to foresee new potential therapeutic avenues.
Topics: Humans; Nitroglycerin; Angina Pectoris; Nitric Oxide; Neoplasms
PubMed: 37173331
DOI: 10.1038/s41419-023-05838-5 -
Hong Kong Medical Journal = Xianggang... Apr 2014The pathogenesis and management of lateral epicondylalgia, or tennis elbow, a common ailment affecting middle-aged subjects of both genders continue to provoke... (Review)
Review
The pathogenesis and management of lateral epicondylalgia, or tennis elbow, a common ailment affecting middle-aged subjects of both genders continue to provoke controversy. Currently it is thought to be due to local tendon pathology, pain system changes, and motor system impairment. Its diagnosis is usually clinical, based on a classical history, as well as symptoms and signs. In selected cases, additional imaging (X-rays, ultrasound, and magnetic resonance imaging) can help to confirm the diagnosis. Different treatment modalities have been described, including the use of orthotics, non-steroidal anti-inflammatory drugs, steroid injections, topical glyceryl trinitrate, exercise therapy, manual therapy, ultrasound therapy, laser therapy, extracorporeal shockwave therapy, acupuncture, taping, platelet-rich plasma injections, hyaluronan gel injections, botulinum toxin injections, and surgery. Nevertheless, evidence to select the best treatment is lacking and the choice of therapy depends on the experience of the management team, availability of the equipment and expertise, and patient response. This article provides a snapshot of current medical practice for lateral epicondylalgia management.
Topics: Acupuncture Therapy; Administration, Topical; Athletic Tape; Botulinum Toxins; Braces; Exercise Therapy; Glucocorticoids; High-Energy Shock Waves; Humans; Hyaluronic Acid; Injections, Intra-Articular; Laser Therapy; Massage; Muscle Strength; Neurotoxins; Nitroglycerin; Orthopedic Procedures; Pain Perception; Physical Examination; Platelet-Rich Plasma; Tennis Elbow; Ultrasonic Therapy; Vasodilator Agents; Viscosupplements
PubMed: 24584568
DOI: 10.12809/hkmj134110 -
British Journal of Pharmacology Sep 2008Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used... (Review)
Review
Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been used clinically since the late nineteenth century for the treatment of coronary artery disease (angina pectoris), congestive heart failure and myocardial infarction. Medline lists more than 15 000 publications on GTN and other organic nitrates, but the mode of action of these drugs is still largely a mystery. In the first part of this article, we give an overview on the molecular mechanisms of GTN biotransformation resulting in vascular cyclic GMP accumulation and vasodilation with focus on the role of mitochondrial aldehyde dehydrogenase (ALDH2) and the link between the ALDH2 reaction and activation of vascular soluble guanylate cyclase (sGC). In particular, we address the identity of the bioactive species that activates sGC and the potential involvement of nitrite as an intermediate, describe our recent findings suggesting that ALDH2 catalyses direct 3-electron reduction of GTN to NO and discuss possible reaction mechanisms. In the second part, we discuss contingent processes leading to markedly reduced sensitivity of blood vessels to GTN, referred to as vascular nitrate tolerance. Again, we focus on ALDH2 and describe the current controversy on the role of ALDH2 inactivation in tolerance development. Finally, we emphasize some of the most intriguing, in our opinion, unresolved puzzles of GTN pharmacology that urgently need to be addressed in future studies.
Topics: Animals; Biotransformation; Drug Tolerance; Humans; Nitrates; Nitroglycerin; United States
PubMed: 18574453
DOI: 10.1038/bjp.2008.263 -
The Journal of Headache and Pain Dec 2022Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only...
BACKGROUND
Calcitonin gene-related peptide (CGRP) antagonizing drugs represents the most important advance in migraine therapy for decades. However, these new drugs are only effective in 50-60% of patients. Recent studies have shown that the pituitary adenylate cyclase-activating peptide (PACAP38) pathway is independent from the CGRP signaling pathway. Here, we investigate PACAP38 signaling pathways in relation to glyceryl trinitrate (GTN), levcromakalim and sumatriptan.
METHODS
In vivo mouse models of PACAP38-, GTN-, and levcromakalim-induced migraine were applied using tactile sensitivity to von Frey filaments as measuring readout. Signaling pathways involved in the three models were dissected using PACAP-inhibiting antibodies (mAbs) and sumatriptan.
RESULTS
We showed that PACAP mAbs block PACAP38 induced hypersensitivity, but not via signaling pathways involved in GTN and levcromakalim. Also, sumatriptan has no effect on PACAP38-induced hypersensitivity relevant to migraine. This is the first study testing the effect of a PACAP-inhibiting drug on GTN- and levcromakalim-induced hypersensitivity.
CONCLUSIONS
Based on the findings in our mouse model of migraine using migraine-inducing compounds and anti-migraine drugs, we suggest that PACAP acts via a distinct pathway. Using PACAP38 antagonism may be a novel therapeutic target of interest in a subgroup of migraine patients who do not respond to existing therapies.
Topics: Animals; Mice; Calcitonin Gene-Related Peptide; Cromakalim; Disease Models, Animal; Migraine Disorders; Nitroglycerin; Pituitary Adenylate Cyclase-Activating Polypeptide; Signal Transduction; Sumatriptan; Drug Hypersensitivity
PubMed: 36471250
DOI: 10.1186/s10194-022-01523-8 -
ChemMedChem Nov 2022Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate-coumarins and evaluated their vasorelaxant activity in...
Due to the need for new chemical entities for cardiovascular diseases, we have synthesized a new series of nitrate-coumarins and evaluated their vasorelaxant activity in contraction-relaxation studies using rat aorta rings precontracted with phenylephrine or by depolarization with a high concentration of potassium chloride. Four of the new compounds were able to relax smooth vascular muscle with a similar profile and potency to glyceryl trinitrate (IC =12.73 nM) and sodium nitroprusside (IC =4.32 nM). Coumarin-7-yl-methyl nitrate (4), the best compound within the series, was able to relax smooth vascular muscle in the low nanomolar range (IC =1.92 nM). The mechanisms of action have been explored, being the activation of sGC and the opening of K channels involved. Our studies indicate that the new nitrate derivatives are reversible and not deleterious for aortic rings, suggesting that these compounds have a potential interest for the development of new and highly efficient vasodilator drugs.
Topics: Animals; Rats; Vasodilator Agents; Nitrates; Muscle, Smooth, Vascular; Nitroglycerin; Coumarins; Nitric Oxide
PubMed: 36109344
DOI: 10.1002/cmdc.202200476 -
The Cochrane Database of Systematic... May 2014A number of tocolytics have been advocated for the treatment of threatened preterm labour in order to delay birth. The rationale is that a delay in birth may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A number of tocolytics have been advocated for the treatment of threatened preterm labour in order to delay birth. The rationale is that a delay in birth may be associated with improved neonatal morbidity or mortality. Nitric oxide donors, such as nitroglycerin, have been used to relax the uterus. This review addresses their efficacy, adverse effects and influence on neonatal outcome.
OBJECTIVES
To determine whether nitric oxide donors administered in threatened preterm labour are associated with a delay in birth, adverse effects or improved neonatal outcome.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 December 2013).
SELECTION CRITERIA
Randomised controlled trials of nitric oxide donors administered for tocolysis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data.
MAIN RESULTS
Twelve trials, including a total of 1227 women at risk of preterm labour, contributed data to this updated review. The methodological quality of trials was mixed; trials comparing nitric oxide donors with other types of tocolytics were not blinded and this may have had an impact on findings.Three studies compared nitric oxide donors (glyceryl trinitrate (GTN)) with placebo. There was no significant evidence that nitric oxide donors prolonged pregnancy beyond 48 hours (average risk ratio (RR) 1.19, 95% confidence interval (CI) 0.74 to 1.90, two studies, 186 women), and although for most adverse effects there was no significant difference between groups, women in the active treatment group in one study were at higher risk of experiencing a headache. For infant outcomes there was no significant evidence that nitric oxide donors reduced the risk of neonatal death or serious morbidity (stillbirth RR 0.36, 95% CI 0.01 to 8.59, one study, 153 infants; neonatal death RR 0.43, 95% CI 0.06 to 2.89, two studies, 186 infants). One study, using a composite outcome, reported a reduced risk of serious adverse outcomes for infants in the GTN group which approached statistical significance (RR 0.29, 95% CI 0.08 to 1.00, 153 infants). Overall, these studies were underpowered to identify differences between groups for most outcomes.When nitric oxide donors were compared with other tocolytic drugs there was no significant evidence that nitric oxide donors performed better than other tocolytics (betamimetics, magnesium sulphate, a calcium channel blocker or a combination of tocolytics) in terms of pregnancy prolongation, although nitric oxide donors appeared to be associated with a reduction in most adverse effects, apart from headache. There was no significant difference between groups for infant morbidity or mortality outcomes.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to support the routine administration of nitric oxide donors in the treatment of threatened preterm labour.
Topics: Female; Humans; Nitric Oxide Donors; Nitroglycerin; Obstetric Labor, Premature; Pregnancy; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents
PubMed: 24809331
DOI: 10.1002/14651858.CD002860.pub2