s-1743 and Inflammation

Using a double-blinded randomized crossover design, this study aimed to evaluate acute postoperative pain management, swelling and trismus in 46 volunteers undergoing extractions of the two lower third molars, in similar positions, at two different appointments who consumed a tablet of either NE (naproxen 500 mg + esomepraz ole 20 mg) or only naproxen (500 mg) every 12 hours for 4 days.. Parameters were analyzed: self-reported pain intensity using a visual analog scale (VAS) pre- and postoperative mouth opening; incidence, type and severity of adverse reactions; total quantity consumed of rescue medication; and pre- and postoperative swelling.. Female volunteers reported significantly more postoperative pain at 1, 1.5, 2, 3 and 4hrs after surgery while also taking their first rescue medication at a time significantly earlier when consuming NE when compared to naproxen (3.7hrs and 6.7hrs). Conversely, no differences were found between each drug group in males.. In conclusion, throughout the entire study, pain was mild after using either drug in both men and women with pain scores on average well below 40mm (VAS), although in women naproxen improved acute postoperative pain management when compared to NE.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Female; Humans; Inflammation; Male; Molar, Third; Naproxen; Pain Management; Pain, Postoperative; Proton Pump Inhibitors; Tooth Extraction; Treatment Outcome; Young Adult

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder with end-organ damage that presents after 20 wk of gestation. PE pathophysiology often includes vascular dysfunction and increased inflammation that continues to damage patient health even after PE resolves. Currently, there is no cure for PE beyond delivery of the fetal-placental unit. Previous clinical studies have identified elevated placental NLRP3 expression in patients with PE and suggest NLRP3 as a potential therapeutic target. In this study, we examined the effect of NLRP3 inhibition on PE pathophysiology in the reduced uterine perfusion pressure (RUPP) model rat using MCC950 (20 mg/kg/day) or esomeprazole (3.5 mg/kg/day). We hypothesized that increased NLRP3 in response to placental ischemia impairs anti-inflammatory IL-33 signaling to induce T-helper 17 cell (T

Topics: Animals; Blood Pressure; Esomeprazole; Female; Humans; Hypertension; Inflammation; Interleukin-33; Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Placenta; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley

Xenobiotics can interact with cytochromes P450 (CYPs), resulting in drug-drug interactions, but CYPs can also contribute to drug-disease interactions, especially in the case of inflammation, which downregulates CYP activities through pretranscriptional and posttranscriptional mechanisms. Interleukin-6 (IL-6), a key proinflammatory cytokine, is mainly responsible for this effect. The aim of our study was to develop a physiologically based pharmacokinetic (PBPK) model to foresee the impact of elevated IL-6 levels in combination with drug interactions with esomeprazole on CYP3A and CYP2C19. Data from a cohort of elective hip surgery patients whose CYP3A and CYP2C19 activities were measured before and after surgery were used to validate the accurate prediction of the developed models. Successive steps were to fit models for IL-6, esomeprazole, and omeprazole and its metabolite from the literature and to validate them. The models for midazolam and its metabolite were obtained from the literature. When appropriate, a correction factor was applied to convert drug concentrations from whole blood to plasma. Mean ratios between simulated and observed areas under the curve for omeprazole/5-hydroxy omeprazole, esomeprazole, and IL-6 were 1.53, 1.06, and 0.69, respectively, indicating an accurate prediction of the developed models. The impact of IL-6 and esomeprazole on the exposure to CYP3A and CYP2C19 probe substrates and respective metabolites were correctly predicted. Indeed, the ratio between predicted and observed mean concentrations were <2 for all observations (ranging from 0.51 to 1.7). The impact of IL-6 and esomeprazole on CYP3A and CYP2C19 activities after a hip surgery were correctly predicted with the developed PBPK models.

Topics: Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Down-Regulation; Drug Interactions; Esomeprazole; Humans; Inflammation; Interleukin-6; Midazolam; Omeprazole

The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg

Topics: Animals; Anti-Ulcer Agents; Apoptosis; Caspase 3; Esomeprazole; Female; Heme Oxygenase-1; Humans; Indomethacin; Inflammation; Intestinal Mucosa; Isothiocyanates; Male; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Signal Transduction; Stomach Ulcer

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy

Topics: Active Transport, Cell Nucleus; Administration, Topical; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Esomeprazole; Fibrosis; Gene Expression Profiling; Heme Oxygenase-1; Humans; Inflammation; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Models, Anatomic; NF-E2-Related Factor 2; Radiodermatitis; Radiotherapy; Skin; Wound Healing

We describe a case report of a patient who developed transient type 2 diabetes after a drug-induced (esomeprazole) sub-acute hepatitis. This case evidences the pathophysiological relevance, also in humans, of liver inflammation in the pathogenesis of type 2 diabetes.

Topics: Anti-Ulcer Agents; Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 2; Esomeprazole; Humans; Inflammation; Insulin Resistance; Male; Middle Aged

Acid reflux is often difficult to control medically.. To assess the effect of 40 mg twice daily esomeprazole (high-dose) on gastric and oesophageal pH and symptoms, and biomarkers relevant to adenocarcinoma, in patients with Barrett's oesophagus (BO).. Eighteen patients, treated with proton pump inhibitors as prescribed by their treating doctor, had their therapy increased to high-dose esomeprazole for 6 months.. At entry into the study, 9/18 patients had excessive 24-h oesophageal acid exposure, and gastric pH remained <4 for >16 h in 8/18. With high-dose esomeprazole, excessive acid exposure occurred in 2/18 patients, and gastric pH <4 was decreased from 38% of overall recording time and 53% of the nocturnal period to 15% and 17%, respectively (P < 0.001). There was a reduction in self-assessed symptoms of heartburn (P = 0.0005) and regurgitation (P < 0.0001), and inflammation and proliferation in the Barrett's mucosa. There was no significant change in p53, MGMT or COX-2 expression, or in aberrant DNA methylation.. High-dose esomeprazole achieved higher levels of gastric acid suppression and control of oesophageal acid reflux and symptoms, with significant decreases in inflammation and epithelial proliferation. There was no reversal of aberrant DNA methylation.

Topics: Adult; Aged; Anti-Ulcer Agents; Barrett Esophagus; Biopsy; Cell Proliferation; DNA Methylation; Esomeprazole; Esophagus; Female; Humans; Hydrogen-Ion Concentration; Inflammation; Male; Middle Aged; Mucous Membrane; Proton Pump Inhibitors; Stomach; Tumor Suppressor Proteins