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The effects of some nonsteroidal anti-inflammatory drugs on experimental induced gastric ulcers in rats.

Celecoxib is a frequently used nonsteroidal anti-inflammatory drug (NSAID) in the treatment of rheumatoid arthritis and osteoarthritis. It selectively inhibits cyclooxygenase II (COX-2) enzyme which is responsible for the production of proinflammatory prostanoids. It has been proposed that since it does not significantly inhibit COX-1, an isoenzyme responsible for the production of cytoprotective prostanoids, celecoxib has fewer side effects in the stomach. Dipyrone which is a drug with potent analgesic activity has no significant inhibitory effect on COX. In this study, the effects of celecox

Elevation of pentylenetetrazole-induced seizure threshold in cholestatic mice: interaction between opioid and cannabinoid systems.

BACKGROUND AND AIM: Several studies have reported that endogenous opioid and cannabinoid systems may be involved in some pathophysiological changes occurring in cholestatic liver disease. It is well known that endogenous opioids and cannabinoids alter the susceptibility of experimental animals to different models of seizure. METHODS: The alterations in pentylenetetrazole-induced clonic seizure thresholds were evaluated from 1 to 6 days after bile duct ligation in mice. Whether the pretreatment of cholestatic mice with different doses of opioid receptor antagonist naltrexone or cannabinoid CB(

Cardiovascular events associated with the use of four nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) versus a cyclooxygenase-2 inhibitor (celecoxib): a population-based analysis in Taiwanese adults.

BACKGROUND: Serious cardiovascular events (CVEs) have been linked to the use of cyclooxygenase (COX)-2 inhibitors, a category of selective NSAIDs. However, few studies are available that have compared the risk for CVEs between COX-2 inhibitors and nonselective NSAIDs in adults undergoing long-term treatment. OBJECTIVES: The present study assessed (1) whether long-term use of nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) is associated with an increased risk for treatment-related CVEs (acute myocardial infarction [AMI], angina, cerebrovascular attack [CVA], and/or transient

The obesity epidemic and its cardiovascular consequences.

PURPOSE OF REVIEW: Obesity has reached global epidemic proportions because of an increasingly obesogenic environment. This review examines the association between obesity, and in particular visceral fat, as a risk factor for cardiovascular disease and mortality. RECENT FINDINGS: The World Health Organization defines obesity based on the body mass index. Recently the waist-to-hip ratio has been shown to be a significantly stronger predictor of cardiovascular events than body mass index. The metabolic syndrome and its evolving definition represent a cluster of metabolic risk factors which help

Efficacy and tolerability of celecoxib compared with diclofenac slow release in the treatment of acute ankle sprain in an Asian population.

INTRODUCTION: Cyclooxygenase (COX)-2 selective inhibitors are attractive candidates for treatment of ankle sprain because of their efficacy as anti-inflammatory and analgesic agents and their overall safety, including lack of effect on platelet aggregation. The objective of this study was to assess the efficacy and tolerability of celecoxib compared with diclofenac slow release (SR) in the treatment of acute ankle sprain in an Asian population. METHODS: In this seven-day, multicentre, double-blind, randomised, parallel-group trial, 370 patients with first- or second-degree ankle sprain occurr

Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies.

OBJECTIVE: To compare efficacy among 1578 patients with osteoarthritis randomized to take acetaminophen 4000 mg (n=269), celecoxib 200 mg (n=523), rofecoxib 12.5 mg (n=259), or rofecoxib 25 mg (n=527) in a double blind trial [Vioxx, Acetaminophen, Celecoxib Trial (VACT2)]. Results were also pooled with the similarly designed VACT1 trial. METHODS: Patients evaluated over Days 1 to 6 and 6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. RESULTS: For VACT2, median time to good or excellent PGART resp

Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib.

OBJECTIVE: To determine the efficacy and safety of lumiracoxib for knee osteoarthritis (OA). METHODS: This was a 13-week, multicentre, randomized, double-blind, double-dummy, placebo-controlled study. Males or females aged >/= 18 years with primary knee OA received lumiracoxib 100 mg od, lumiracoxib 100 mg od with a loading dose of 200 mg od for the first two weeks, celecoxib 200 mg od, or placebo. MAIN OUTCOME MEASURES: Co-primary variables, assessed at week 13, were OA pain intensity in the target knee, patient's global assessment of disease activity and the WOMAC total score. Other variab

The cannabinoid receptor antagonist SR 141716 attenuates overfeeding induced by systemic or intracranial morphine.

RATIONALE: Considerable interplay exists between the brain's opioid and cannabinoid systems. These systems are both involved in the control of appetite and research supports the notion that the opioid system modulates the role of the cannabinoid system on appetite. However, the ability of the cannabinoid system to modulate the opioid system's control over appetite has not been well studied. OBJECTIVES: The present study examined the role of cannabinoid CB(1) receptors in the control of opioid-induced feeding, and sought to identify specific brain regions underlying this role. METHODS: After

The efficacy of premedication with celecoxib and acetaminophen in preventing pain after otolaryngologic surgery.

UNLABELLED: Non-opioid analgesics are often used to supplement opioids for the management of perioperative pain. In this randomized, double-blinded, placebo-controlled study, we examined the effects of acetaminophen and a cyclooxygenase type-2 inhibitor, celecoxib, when administered alone or in combination, before elective otolaryngologic surgery in 112 healthy outpatients. Subjects were assigned to 1 of 4 study groups: Group 1, placebo (vitamin C, 500 mg per os [PO]); Group 2, acetaminophen 2000 mg PO; Group 3, celecoxib 200 mg PO; or Group 4, acetaminophen 2000 mg and celecoxib 200 mg PO. Al

Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery.

UNLABELLED: Nonsteroidal antiinflammatory drugs are recommended for the multimodal management of postoperative pain and may have a significant opioid-sparing effect after major surgery. The analgesic efficacy of the cyclooxygenase-2 nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, have not been evaluated after major orthopedic surgery. This study was designed to determine whether the administration of a preoperative dose of celecoxib or rofecoxib to patients who have undergone spinal stabilization would decrease patient-controlled analgesia (PCA) morphine use and/or enhance analge

A role for central cannabinoid and opioid systems in peripheral delta 9-tetrahydrocannabinol-induced analgesia in mice.

delta 9-tetrahydrocannabinol elicits analgesia in rodents by both spinal and supraspinal mechanisms. Pharmacological data point to a link between cannabinoids and the opioid system. The lack of specific cannabinoid receptor antagonists has hindered the investigation of the physiological relevance of the cannabinoid system in nociception control. In this work we characterized the effect of the new cannabinoid receptor antagonist, SR-141,716 A (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3- pyrazolecarboxamide hydrochloride), on delta 9-tetrahydrocannabinol-induced analgesia.

Effects of selected anti-tumor-promoting chemicals on metabolic cooperation between Chinese hamster V79 cells.

Many tumor-promoting chemicals inhibit gap junctional communication between cells. We investigated the possibility that antipromoting chemicals may act inversely and enhance gap junctional communication. The V79/metabolic cooperation assay is an in vitro test that measures gap junctional communication indirectly by determining the extent of metabolic cooperation between mutant and wild-type V79 Chinese hamster lung fibroblasts in culture. Six in vivo antipromoters (caffeine, 3-isobutyl-1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenylalanine chloromethyl ketone (TPCK), and a

Inhibitors of the lipoxygenase pathway specifically block orthopoxvirus replication.

Inhibitors of arachidonic acid metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA), BW755c, and nordihydroguaiaretic acid were found to specifically interfere with the replication of cowpox virus (an orthopoxvirus) both in vivo and in vitro. Further studies in vitro showed that the drugs ETYA and BW755c were effective in inhibiting the replication of two additional orthopoxviruses, ectromelia and vaccinia viruses, but not human parainfluenza virus-3. In ETYA-treated and cowpox virus-infected cells, early and late gene expression were near normal levels, whereas the assembly of virus-specific me

Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.

Transforming growth factor-beta (TGF-β) signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate) is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically

Совпадение в полном тексте источника
… Characterization or Substituted Pyrazoles as ATP-Competitive TGF-beta Receptor Kinase Inhibitors: the TGF-beta superfamily. La Jolla (CA): American Association for Cancer Research; 2003. 53. Peng SB, Yan L, Xia X, et al. … Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry. 2005;44(7):2293–2304. doi: 10.1021/bi048851x. 54. Muraoka-Cook RS, Shin I, Yi JY, et al. …

Protective Effects of Riociguat Against Contrast-Induced Nephropathy: An Experimental and Machine Learning-Based Study in Rats.

Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury following exposure to iodinated contrast media, and effective preventive strategies remain limited. This study investigated the renoprotective effects of riociguat, a soluble guanylate cyclase stimulator, in an experimental rat model of CIN and explored machine-learning-based prediction of renal injury using histopathological, biochemical, and inflammatory markers. Thirty-six female Wistar albino rats were randomized into control, riociguat, CIN model, and CIN + riociguat groups. CIN was induced by iohexol after de

Safety and efficacy of elexacaftor/tezacaftor/ivacaftor in adolescents and adults with cystic fibrosis and F508del-gating and F508del-residual function genotypes: results from an open-label extension study.

RATIONALE: In an 8-week, active-controlled, phase 3 study (445-104), elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in participants ≥ 12 years of age with cystic fibrosis (CF) and F508del-gating (F/G) or F508del-residual function (F/RF) genotypes, conferring additional clinical benefits relative to IVA and TEZ/IVA. Participants who completed this 8-week parent study continued to an open-label extension. OBJECTIVE: To assess the long-term safety and efficacy of ELX/TEZ/IVA in adolescents and adults with CF and F/G or F/RF genotypes. METHODS: This 2-part (P

Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.

PURPOSE: Rearranged during transfection (RET) alterations are oncogenic drivers across solid tumors. Selective RET inhibitors (SRI) selpercatinib and pralsetinib have transformed outcomes for patients with RET-altered malignancies. Limited knowledge exists on genomic mechanisms of resistance to SRI. EXPERIMENTAL DESIGN: We established "RETgistry," a global consortium of patients with advanced RET-altered solid tumors who received SRI and underwent postprogression tissue or plasma biopsies assessed by next-generation sequencing. Frequencies of secondary RET resistance mutations and acquired no

Haemodynamic and clinical impacts of switching phosphodiesterase-5 inhibitors to riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after balloon pulmonary angioplasty (BPA) - a prospective cohort study.

BACKGROUND: For patients with chronic thromboembolic pulmonary hypertension (CTEPH), balloon pulmonary angioplasty (BPA) has been associated with superior reductions in mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) when compared to riociguat. In patients with pulmonary arterial hypertension (PAH), greater clinical improvements were observed after switching from phosphodiesterase-5 inhibitors (PDE5i) to riociguat. However, the impact of transitioning from PDE5i to riociguat on pulmonary haemodynamics and functional outcomes after BPA remains unclear. METHODS: Th

Debio 0123, a WEE1 kinase inhibitor: Phase 1 results from dose escalation in patients with advanced solid tumors.

PURPOSE: The DNA damage-activated G2/M and S phase cell cycle checkpoint regulator WEE1 kinase is an attractive therapeutic target for solid tumors. We report the results of the dose escalation part of a phase 1 trial assessing the WEE1 inhibitor Debio 0123. PATIENTS AND METHODS: The study enrolled patients with relapsed/refractory advanced solid tumors. Debio 0123 was given orally, once daily. Safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics were assessed. RESULTS: Twenty-seven patients were treated with Debio 0123 at doses ranging from 30 to 350 mg. Any grade