Abstract：
:In this investigation we have examined the effects of indomethacin, an inhibitor of the cyclooxygenase pathway of arachidonic acid, upon the kinetics of the release of tumour necrosis factor alpha (TNF) and of the expression of TNF gene by lipopolysaccharide (LPS)-stimulated human blood monocytes (BM). Following stimulation of BM with LPS, TNF was released within 2 h, reached peak values at 8 h and declined at subsequent time-points (24 and 48 h). Indomethacin (10(-5) M) slightly stimulated the production of TNF at 2, 4, and 8 h and prevented the decline of TNF observed at 24 and 48 h. This effect was related to the persistence of TNF synthesis, as demonstrated by kinetic evaluation of the expression of TNF gene performed by dot-blot analysis. The effects of indomethacin on TNF release and TNF gene expression were due to the inhibition of endogenous prostaglandin (PG)E2 production. In the absence of indomethacin, PGE2 release by the LPS-stimulated BM began concomitantly with the decline of TNF production by the same cells under the same stimulus. Indomethacin completely blocked PGE2 release at any time-point. Exogenous PGE2 suppressed the release of TNF and the expression of TNF gene in a dose-dependent fashion. Exogenous PGE2 completely reversed the effects of indomethacin on TNF production at 24 h. These findings suggest that indomethacin may significantly alter the kinetics of TNF release and TNF gene expression by LPS-stimulated BM. These effects are related, at least in part, to the inhibition of the production of endogenous PGE2, an important self-driven regulatory factor of the kinetics of TNF production.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Spatafora M,Chiappara G,D'Amico D,Volpes D,Melis M,Pace E,Merendino Adoi
10.1016/s1043-6618(05)80084-2subject
Has Abstractpub_date
1991-04-01 00:00:00pages
247-57issue
3eissn
1043-6618issn
1096-1186pii
S1043-6618(05)80084-2journal_volume
23pub_type
杂志文章abstract：:The aim of this review is to underline the redundancy of down-regulation pathways for p53, at the light of the two more important degradative systems: calpains and ubiquitin-dependent pathways. The MDM2 feed-back loop is also illustrated, as well as the phosphorylative/dephosphorylative regulation of the latent and ac...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1006/phrs.1997.0269
更新日期：1998-02-01 00:00:00
abstract：:The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0530
更新日期：1999-10-01 00:00:00
abstract：:Tumor metastasis is a key cause of cancer mortality, and inhibiting migration of cancer cells is one of the major directions of anti-metastatic drug development. Calumenin and fibulin-1 are two extracellular proteins that synergistically inhibit cell migration and tumor metastasis, and could potentially be served as t...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2015.05.001
更新日期：2015-09-01 00:00:00
abstract：:As the body's first line of defense, the skin is the organ most frequently exposed to chemicals present in personal hygiene products, household products, or materials used in the work environment. In this context, skin disorders account for more than 40 % of all occupational and work-related diseases, constituting a s...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105282
更新日期：2020-12-01 00:00:00
abstract：:In the present study, we have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of the NMDA receptor and GABA(A)receptor binding in rat brain. The NMDA receptor binding was analysed by quantitative autoradiography using [(3)H]MK-801 binding, and the GABA(A)receptor bindings we...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0809
更新日期：2001-05-01 00:00:00
abstract：:Exogenously administered fructose-1,6-diphosphate (FDP) has been studied for its ability to protect tissue during hypoxia or ischemia. Recently, a clear effect of FDP on the central nervous system has raised the question whether FDP can get into the brain. FDP levels were measured in blood, brain, liver, kidney, muscl...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2008.01.008
更新日期：2008-03-01 00:00:00
abstract：:Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the ana...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0921
更新日期：2002-02-01 00:00:00
abstract：:Erdosteine was introduced in the market as a mucolytic agent for chronic pulmonary diseases more than 10 years ago. The drug contains two blocked sulphydryl groups one of which, after hepatic metabolization and opening of the thiolactone ring, becomes available both for the mucolytic and free radical scavenging and an...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2006.12.006
更新日期：2007-04-01 00:00:00
abstract：:In the present study we evaluated the protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological an...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80067-2
更新日期：1992-01-01 00:00:00
abstract：:Cocoa contains flavonoids with antioxidant properties. The aim of this study was to ascertain the effect of cocoa intake on oxidative stress associated with a model of chronic inflammation such as adjuvant arthritis. Female Wistar rats were fed with a 5% or 10% cocoa-enriched diet or were given p.o. a quercetin suspen...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2012.05.009
更新日期：2012-09-01 00:00:00
abstract：:Recent studies have shown that a higher consumption of green tea leads to a lower prevalence of depressive symptoms in elderly individuals. However, no studies have explored the antidepressant-like effect of green tea in preclinical models of depression. The aim of this study was to investigate the antidepressant-like...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.09.007
更新日期：2012-01-01 00:00:00
abstract：:Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interes...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1006/phrs.1998.0288
更新日期：1998-03-01 00:00:00
abstract：:In this study, we have investigated the vasodilator response to acetylcholine under diabetic conditions in isolated renal arteries of Wistar rats. The effect of nitric oxide synthase (NOS) inhibition on acetylcholine-induced vasodilator response was investigated. We have also examined the effects of two endothelium-de...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(03)00109-9
更新日期：2003-09-01 00:00:00
abstract：:The antinociceptive and motor effects of the hydrophilic alpha 2-adrenoceptor agonist ST-91 were studied after intrathecal administration to male Wistar rats in different heat-pain tests and different test settings. Intrathecal administration of ST-91 caused a dose-dependent increase in hind paw licking latency in the...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0188
更新日期：1997-06-01 00:00:00
abstract：:Myriocin, a potent inhibitor of serine palmitoyltransferase (SPT), has been shown to reduce plasma sphingolipids, cholesterol and triglycerides in hyperlipidemic apolipoprotein E knockout (apoE KO) mice. We hypothesized that the inhibition of sphingolipid biosynthesis modulates the composition of atherosclerotic plaqu...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2008.06.005
更新日期：2008-07-01 00:00:00
abstract：:Indole-based compounds, such as the alkyl-indole (AI) compound WIN55212-2, activate the cannabinoid receptors, CB1 and CB2, two well-characterized G protein-coupled receptors (GPCR). Reports indicate that several indole-based cannabinoid agonists, including WIN55212-2, lack selectivity and interact with at least two a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.10.025
更新日期：2017-01-01 00:00:00
abstract：:Aminoglycoside antibiotics are employed clinically because of their potent bactericidal activities, less bacterial resistance, post-antibiotic effects and low cost. However, drugs belong to this class are well-known to cause nephrotoxicity, which limits their frequent clinical exploitation. Gentamicin, a commonly used...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2010.04.004
更新日期：2010-09-01 00:00:00
abstract：:Reproductive dysfunction in the female diabetic rat is associated with impaired hypothalamic-hypophyseal system, anovulation, insufficiency of ovarian steroidogenesis and spontaneous failure of pregnancy. Formation of decidua, the highly modified endometrium of pregnancy and pseudopregnancy could only be achieved when...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2000.0673
更新日期：2000-08-01 00:00:00
abstract：:This study was performed in order to investigate the cholinomimetic response of seminal vesicles isolated from rats treated with hydrocortisone acetate during perinatal life. At the adult phase, the body weight and the wet weight of the seminal vesicle of these animals were unchanged. However, these male rats exhibite...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：
更新日期：2003-07-01 00:00:00
abstract：:Leishmaniases are severe vector-borne diseases affecting humans and animals, caused by Leishmania protozoans. Over one billion people and millions of dogs live in endemic areas for leishmaniases and are at risk of infection. Immune polarization plays a major role in determining the outcome of Leishmania infections: ho...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105288
更新日期：2020-11-01 00:00:00
abstract：:Asthma and COPD make up the majority of obstructive airways diseases (OADs), which affects ∼11 % of the population. The main drugs used to treat OADs have not changed in the past five decades, with advancements mainly comprising variations on existing treatments. The recent biologics are beneficial to only specific su...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105029
更新日期：2020-09-01 00:00:00
abstract：:The clear importance of mutated KRAS as a therapeutic target has driven the investigation of multiple approaches to inhibit oncogenic KRAS signaling at different molecular levels. However, no KRAS-targeted therapy has reached the clinic to date, which underlies the intrinsic difficulty in developing effective, direct ...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.01.006
更新日期：2017-03-01 00:00:00
abstract：:MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression by targeting specific mRNAs for degradation or translation repression. Changes in miRNAs expression profiles have been reported in several neurodegenerative disorders such as Alzheimer's disease (AD) and related tauopathies...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.104729
更新日期：2020-05-01 00:00:00
abstract：:Erectile function is a widely accepted indicator of systemic endothelial activity since from a clinical standpoint erectile dysfunction (ED) often precedes cardiovascular events. Recently it has been described a potential role for β3 adrenoceptor in cardiovascular diseases emphasizing a possible development of new dru...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2017.07.025
更新日期：2017-10-01 00:00:00
abstract：:Implantable cardioverter-defibrillators (ICDs) have revolutionized the primary and secondary prevention of patients with ventricular arrhythmias. However, the adverse effects of appropriate or inappropriate shocks may require the adjunctive use of anti-arrhythmic drugs (AADs). Beta blockers are the cornerstone of phar...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.03.020
更新日期：2019-05-01 00:00:00
abstract：:Evodiae fructus is a widely used herbal drug in traditional Chinese medicine. Evodia extract was found to inhibit hERG channels. The aim of the current study was to identify hERG inhibitors in Evodia extract and to investigate their potential proarrhythmic effects. Dehydroevodiamine (DHE) and hortiamine were identifie...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2018.02.024
更新日期：2018-05-01 00:00:00
abstract：:A major focus of contemporary drug screening strategies is the identification of novel anticancer compounds, which often results in underutilization of resources. Current drug evaluation involves in vivo tumor (xenograft) regression as proof-of-principle for cytotoxicity (POC). However, this end-point lacks any assess...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.07.018
更新日期：2016-09-01 00:00:00
abstract：:Despite our insufficient understanding of the exact molecular mechanisms of general anesthetics and sedatives, every year millions of children are treated with these drugs in a seemingly safe manner. However, increasing evidence particularly from animal studies has suggested the possibility for deleterious effects in ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2011.10.001
更新日期：2012-03-01 00:00:00
abstract：:The concentration of five lipid-soluble antioxidants (gamma- and alpha-tocopherol, lycopene, beta-carotene and ubiquinol-10) was measured in plasma and very low-density, low-density and high-density lipoproteins (VLDL, LDL and HDL) isolated from young healthy normo- cholesterolemic subjects. Alpha-tocopherol was the e...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0552
更新日期：2000-01-01 00:00:00
abstract：:Several studies have demonstrated that any beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), of which simvastatin (Merck Sharp & Dohme) is an example, on coronary events are linked to their hypocholesterolemic properties. The in vivo effects of simvastatin treatment ...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1006/phrs.2000.0787
更新日期：2001-04-01 00:00:00
