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Neurotherapeutics : the Journal of the... Apr 2021Prostaglandin-E (PGE), an important mediator of inflammation, achieves its functions via four different G protein-coupled receptors (EP1, EP2, EP3, and EP4). We...
Prostaglandin-E (PGE), an important mediator of inflammation, achieves its functions via four different G protein-coupled receptors (EP1, EP2, EP3, and EP4). We previously demonstrated that the EP2 receptor plays a proinflammatory and neurodegenerative role after status epilepticus (SE). We recently developed TG8-260 as a second-generation highly potent and selective EP2 antagonist. Here, we investigate whether TG8-260 is anti-inflammatory and combats neuropathology caused by pilocarpine-induced SE in rats. Adult male Sprague-Dawley rats were injected subcutaneously with pilocarpine (380-400 mg/kg) to induce SE. Following 60 min of SE, the rats were administered three doses of TG8-260 or vehicle and were allowed to recover. Neurodegeneration, neuroinflammation, gliosis, and blood-brain barrier (BBB) integrity were examined 4 days after SE. The results confirmed that pilocarpine-induced SE results in hippocampal neurodegeneration and a robust inflammatory response that persists days after SE. Furthermore, inhibition of the EP2 receptor by TG8-260 administered beginning 2 h after SE significantly reduced hippocampal neuroinflammation and gliosis but, in distinction to the earlier generation EP2 antagonist, did not mitigate neuronal injury or BBB breakdown. Thus, attenuation of neuroinflammation and gliosis is a common feature of EP2 inhibition following SE.
Topics: Animals; Cell Line; Dose-Response Relationship, Drug; Gliosis; Humans; Inflammation Mediators; Male; Mice; Neuroinflammatory Diseases; Pilocarpine; Prostaglandin Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E, EP2 Subtype; Status Epilepticus
PubMed: 33410110
DOI: 10.1007/s13311-020-00969-5 -
Clinical Cardiology May 1981In parallel with experimental research into methods for salvage of ischemic myocardium after acute myocardial infarction (AMI) over the last decade, there has been a... (Review)
Review
In parallel with experimental research into methods for salvage of ischemic myocardium after acute myocardial infarction (AMI) over the last decade, there has been a growing interest in prostaglandins (PG) and their inhibition by aspirin-like drugs or nonsteroidal anti-inflammatory drugs (NSAID). The finding of enhanced PG release during myocardial ischemia and its blockade by the NSAID indomethacin led to the hypothesis that PG might influence the infarction process. Because PG differ in vasoactive, cellular, and metabolic properties, and PG inhibitors also differ in their ability to inhibit synthesis of different PG and their metabolites, some PG inhibitors might be expected to reduce myocardial ischemic injury and infarct size. In addition, the NSAID may directly modify cellular events during infarction. Experiments with NSAID in the anesthetized and conscious animals have demonstrated a reduction of myocardial infarct size with ibuprofen, but an increase in infarct size with indomethacin. The opposite effects of these agents on infarct size might have been related to the different doses used, different degrees of inhibition of PG and their metabolites, and different effects on factors influencing myocardial oxygen supply and demand, metabolic and cellular events during infarction. It has recently been suggested that some of these agents might also influence the healing process after AMI and, therefore, late complications.
Topics: Acute Disease; Animals; Aspirin; Coronary Disease; Humans; Ibuprofen; Indomethacin; Models, Biological; Myocardial Infarction; Prognosis; Prostaglandin Antagonists; Prostaglandins
PubMed: 7021033
DOI: 10.1002/clc.4960040302 -
Medicine Jul 2018There are various etiologies of erectile dysfunction (ED), including endothelial dysfunction, atherosclerosis, and chronic inflammation. Aspirin has a protective role... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
There are various etiologies of erectile dysfunction (ED), including endothelial dysfunction, atherosclerosis, and chronic inflammation. Aspirin has a protective role against endothelial dysfunction and atherosclerosis, whease all non-steroidal anti-inflammatory drugs (NSAIDs) are known for their anti-inflammatory properties. However, association between the use of aspirin or non-aspirin NSAIDs and ED is controversial. Therefore, we reviewed this relationship.
METHODS
We systematically reviewed the pathophysiology of ED, physiological effect of prostaglandins, pharmacological action of NSAIDs, and clinical and basic research studies that evaluated the effect of aspirin or non-aspirin NSAIDs on ED.
RESULTS
The research studies that assessed association between aspirin or non-aspirin NSAIDs are limited, and only 12 articles have been published. One clinical and three basic studies have claimed that aspirin or non-aspirin NSAIDs are beneficial for ED by preserving nitric oxide synthase impairment or penile blood hypercoagulability. One basic and two clinical studies considered them as risk factors because they interfered with prostaglandin production. By contrast, four clinical studies showed irrelevant results after controlling various medical indications. In addition, the mechanical effect of aspirin or non-aspirin NSAIDs on the nitric oxide pathway is still controversial.
CONCLUSIONS
The available research studies revealed that association between aspirin or non-aspirin NSAIDs and ED is controversial. Considering the high frequency of drug use, further clinical and basic investigations should be conducted to clarify their exact relationship.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Erectile Dysfunction; Humans; Male; Nitric Oxide; Penis; Prostaglandin Antagonists; Prostaglandins; Risk Factors
PubMed: 29995772
DOI: 10.1097/MD.0000000000011367 -
African Journal of Traditional,... 2011Dysmenorrhea is painful menstrual cramps, which negatively impacts the quality of life of a large percentage of the world's female population in reproductive age. The... (Review)
Review
Dysmenorrhea is painful menstrual cramps, which negatively impacts the quality of life of a large percentage of the world's female population in reproductive age. The paper reviews the plants used in the Malian traditional medicine for the treatment of dysmenorrhea. Some medicinal plants were effective for treatments of dysmenorrhea with minimal side effects. Conventional therapy for dysmenorrhea, which usually includes non-steroidal anti-inflammatory drugs (NSAIDs), provides symptomatic relief, but presents increasing adverse effects with long-term use. This article is in the framework of a study supported by International Foundation for Science (IFS) on three medicinal plants used in the treatment of dysmenorrhea in Mali: Maytenus senegalensis Stereospermum kunthianum and Trichilia emetica.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Bignoniaceae; Dysmenorrhea; Female; Humans; Mali; Maytenus; Medicine, African Traditional; Meliaceae; Phytotherapy; Plant Extracts; Plants, Medicinal; Prostaglandin Antagonists
PubMed: 22754061
DOI: 10.4314/ajtcam.v8i5S.4 -
Vascular Health and Risk Management 2009Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated... (Review)
Review
Although statins reduce cardiovascular morbidity and mortality further risk reduction is needed. In this respect low HDL-cholesterol concentrations and/or elevated triglyceride concentrations may be potential treatment targets. Niacin (nicotinic acid) is an effective drug which increases the plasma concentration of high-density lipoprotein (HDL)-cholesterol and decreases the concentration of low-density lipoprotein (LDL)-cholesterol, triglycerides and lipoprotein(a). Clinical studies indicate that niacin can significantly reduce the risk for cardiovascular events. However, niacin is not very commonly used because of significant side effects (especially flushing). Laropiprant is a potent selective antagonist of PGD2-receptor subtype-1 and can thus reduce niacin-induced flushing. Although the addition of laropiprant will reduce the frequency of flushing, it will not completely eliminate this side effect. Laropiprant does not change the effect of niacin on lipids or other side effects of niacin (ie, gastro-intestinal problems, glucose elevation). The combination of niacin with laropiprant may therefore enable use of niacin at higher doses and therefore exploit the full potential of the drug. Endpoint studies that will be published over the next few years will show whether this treatment modality also translates into clinical effect in patients treated with statins. Until publication of these studies niacin/laropiprant should be used only in high-risk patients not achieving lipid goals on statins.
Topics: Biomarkers; Cholesterol, HDL; Cholesterol, LDL; Drug Combinations; Dyslipidemias; Flushing; Humans; Hypercholesterolemia; Hypolipidemic Agents; Indoles; Lipids; Lipoprotein(a); Niacin; Receptors, Immunologic; Receptors, Prostaglandin; Treatment Outcome; Triglycerides
PubMed: 20016845
DOI: 10.2147/vhrm.s4502 -
Clinical Cancer Research : An Official... Sep 2012Surgery is a crucial intervention in most cancer patients, but the perioperative period is characterized by increased risks for future outbreak of preexisting... (Review)
Review
Surgery is a crucial intervention in most cancer patients, but the perioperative period is characterized by increased risks for future outbreak of preexisting micrometastases and the initiation of new metastases-the major cause of cancer-related death. Here we argue that the short perioperative period is disproportionately critical in determining long-term recurrence rates, discuss the various underlying risk factors that act synergistically during this period, and assert that this time frame presents an unexplored opportunity to reduce long-term cancer recurrence. We then address physiologic mechanisms that underlie these risk factors, focusing on excess perioperative release of catecholamines and prostaglandins, which were recently shown to be prominent in facilitating cancer recurrence through their direct impact on the malignant tissue and its microenvironment, and through suppressing antimetastatic immunity. The involvement of the immune system is further discussed in light of accumulating evidence in cancer patients, and given the recent identification of endogenously activated unique leukocyte populations which, if not suppressed, can destroy autologous "immune-resistant" tumor cells. We then review animal studies and human correlative findings, suggesting the efficacy of blocking catecholamines and/or prostaglandins perioperatively, limiting metastasis and increasing survival rates. Finally, we propose a specific perioperative pharmacologic intervention in cancer patients, based on simultaneous β-adrenergic blockade and COX-2 inhibition, and discuss specific considerations for its application in clinical trials, including our approved protocol. In sum, we herein present the rationale for a new approach to reduce long-term cancer recurrence by using a relatively safe, brief, and inexpensive intervention during the perioperative period.
Topics: Adrenergic beta-Antagonists; Animals; Catecholamines; Humans; Immunity, Cellular; Neoplasm Metastasis; Neoplasms; Perioperative Period; Prostaglandin Antagonists; Prostaglandins; Recurrence; Treatment Outcome
PubMed: 22753587
DOI: 10.1158/1078-0432.CCR-12-1087 -
Revista de Saude Publica Feb 2012To identify the main counterfeit drugs seized by the Brazilian Federal Police and the states where seizures have been made.
OBJECTIVE
To identify the main counterfeit drugs seized by the Brazilian Federal Police and the states where seizures have been made.
METHODS
A retrospective descriptive study on expert reports produced by criminal investigators of the Federal Police between January 2007 and September 2010, in relation to counterfeit drugs, was carried out.
RESULTS
The drugs with greatest numbers of seizures were selective phosphodiesterase-5 inhibitors that are used for treating male erectile dysfunction (Cialis® and Viagra®, mean = 66% ), followed by anabolic steroids (Durateston® and Hemogenin®: 8.9% and 5.7%, respectively). The greatest proportions of the counterfeit drugs were seized in the states of Paraná, Santa Catarina (both Southeastern Brazil) and São Paulo (Southeastern), and the number of non-authentic drugs sent for investigation increased by more than 200% over the study period. There were increases in seizures of smuggled drugs found together with counterfeit drugs: 67% of the seizures included at least one smuggled drug.
CONCLUSIONS
Counterfeiting of drugs is a severe public health problem. Identification of the classes of counterfeit drugs present in Brazil and the main Brazilian states with this problem may facilitate future preventive and suppressive actions by the Brazilian bodies responsible for such actions.
Topics: Anabolic Agents; Brazil; Counterfeit Drugs; Databases, Factual; Drug and Narcotic Control; Federal Government; Fraud; Government Agencies; Humans; Phosphodiesterase 5 Inhibitors; Police; Prostaglandin Antagonists; Retrospective Studies
PubMed: 22218762
DOI: 10.1590/s0034-89102012005000005 -
British Journal of Pharmacology Feb 19891. BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti-aggregatory concentration-effect curves to...
1. BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti-aggregatory concentration-effect curves to BW 245C were displaced in a parallel manner. The shifts accorded with a Schild plot slope of unity and a pKB of 9.26. 2. Inhibition of platelet aggregation by prostaglandin D2 (PGD2) was antagonized with a similar potency, as were the relaxation effects of BW 245C and PGD2 in the rabbit jugular vein. BW A868C can, therefore, be classified as a DP-receptor antagonist. 3. Actions of BW A868C at other prostaglandin receptors (IP, EP1, EP2, TP and FP) were excluded at concentrations up to 1,000 times higher than the DP-receptor affinity. 4. Analyses of BW 245C- and PGD2-mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C. In rabbit jugular vein a resistant phase of agonism was detectable, indicating that both agonists exerted effects through another receptor (possibly EP2). Also, PGD2, in addition to its anti-aggregatory effect on platelets, demonstrated a pro-aggregatory action in the presence of BW A868C. 5. The contractile effects of PGD2 in guinea-pig tracheal strips were resistant to 10 microM BW A868C indicating that they were not mediated through DP-receptors. 6. To our knowledge this is the first account of a well-classified competitive antagonist at the DP-receptor. Its potency and selectivity make it an important new tool in prostanoid receptor classification and identification.
Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Blood Platelets; Blood Vessels; Guinea Pigs; Humans; Hydantoins; In Vitro Techniques; Jugular Veins; Male; Muscle Contraction; Platelet Aggregation; Prostaglandin D2; Prostaglandin Endoperoxides, Synthetic; Rabbits; Receptors, Prostaglandin; Sulfonamides; Trachea
PubMed: 2924081
DOI: 10.1111/j.1476-5381.1989.tb11816.x -
Frontiers in Bioscience (Scholar... Jun 2010Environmental heat exposure represents one of the most deadly natural hazards in the United States. Heat stroke is a life-threatening illness that affects all segments... (Review)
Review
Environmental heat exposure represents one of the most deadly natural hazards in the United States. Heat stroke is a life-threatening illness that affects all segments of society with few effective treatment strategies to mitigate the long-term debilitating consequences of this syndrome. Although the etiologies of heat stroke are not fully understood, the long-term sequelae are thought to be due to a systemic inflammatory response syndrome (SIRS) that ensues following heat-induced tissue injury. Endotoxin and cytokines have been implicated as key mediators of the heat-induced SIRS, based almost exclusively on correlative data that show high circulating concentrations of these substances in heat stroke patients and animal models. However, endotoxin and cytokine neutralization studies have not consistently supported this hypothesis indicating that the mechanisms of heat stroke morbidity / mortality remain poorly understood. This review discusses the current understanding of the role of endotoxin and cytokines in heat-induced SIRS. Insight is provided into genetic conditions that may predispose to heat stroke and potential therapeutic strategies that may be efficacious against the adverse consequences of this debilitating illness.
Topics: Animals; Cytokines; Disease Models, Animal; Endotoxins; Erythropoietin; Genetic Predisposition to Disease; Glucocorticoids; Heat Stroke; Hot Temperature; Humans; Hypothermia, Induced; Malignant Hyperthermia; Mutation; Polymorphism, Genetic; Prostaglandin Antagonists; Protein C; Recombinant Proteins; Signal Transduction; Systemic Inflammatory Response Syndrome
PubMed: 20515834
DOI: 10.2741/s111 -
Canadian Journal of Comparative... Jul 1977Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory... (Review)
Review
Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.
Topics: Anaphylaxis; Animals; Anti-Inflammatory Agents; Arthritis; Ascariasis; Aspirin; Cattle; Cattle Diseases; Diethylcarbamazine; Guinea Pigs; Horse Diseases; Horses; Hypersensitivity; Indomethacin; Inflammation; Kinins; Leukocytes; Meclofenamic Acid; Phagocytosis; Phenylbutazone; Pneumonia, Atypical Interstitial, of Cattle; Prostaglandin Antagonists; SRS-A
PubMed: 332290
DOI: No ID Found