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https://www.readbyqxmd.com/read/28748412/pharmacokinetics-of-dfn-15-a-novel-oral-solution-of-celecoxib-versus-celecoxib-400-mg-capsules-a-randomized-crossover-study-in-fasting-healthy-volunteers
#1
Arindam Pal, Srinivas Shenoy, Anirudh Gautam, Sagar Munjal, Jing Niu, Mathangi Gopalakrishnan, Joga Gobburru
BACKGROUND: COX-2 inhibitors can be effective for acute migraine, but none is supplied in a rapidly absorbed, ready-to-use oral liquid formulation. DFN-15, a novel oral liquid formulation of celecoxib, is being developed for the acute treatment of migraine with or without aura. Clinical studies with this formulation are ongoing. OBJECTIVES: The objectives of the present study were to compare the bioavailability of DFN-15 with that of the commercial formulation of celecoxib 400-mg oral capsules (Celebrex(®)) and to determine the dose proportionality of DFN-15 in healthy fasted volunteers...
July 26, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28743626/the-roles-of-nf-%C3%AE%C2%BAb-and-ros-in-regulation-of-pro-inflammatory-mediators-of-inflammation-induction-in-lps-stimulated-zebrafish-embryos
#2
Eun-Yi Ko, Su-Hyeon Cho, Seung Hae Kwon, Chi-Yong Eom, Myeong Seon Jeong, WonWoo Lee, Seo-Young Kim, Soo-Jin Heo, Ginnae Ahn, Kang Pa Lee, You-Jin Jeon, Kil-Nam Kim
In this study, the roles of reactive oxygen species (ROS) and NF-κB on inflammation induction in lipopolysaccharide (LPS)-stimulated zebrafish embryos were evaluated using N-acetyl-l-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), specific inhibitors of ROS and NF-κB, respectively. LPS-stimulated zebrafish embryos showed increasing production of NO and ROS and expression of iNOS and COX-2 protein, compared to a control group without LPS. However, NAC significantly inhibited production of NO and ROS and markedly suppressed expression of iNOS and COX-2 protein in LPS-stimulated zebrafish embryos...
July 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28742579/a-review-of-the-epigenetic-contributions-to-endometriosis
#3
Frances W Grimstad, Alan Decherney
Epigenetic influences have been postulated to affect the course of endometriosis. DNA methyltransferases, estrogen and progesterone receptors, micro-RNAs, and histone deacetylators, have shown differential expression in endometriosis compared with normal endometrium. Others such as aromatase, Steroid Factor-1, COX-2, and Homeobox A10 also have epigenetic modifications in endometriosis. Limitations in this area of research include heterogeneity in study design, patient populations, and methods of analysis. Larger, controlled studies are needed...
September 2017: Clinical Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28742280/clinical-outcomes-in-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-in-south-western-sydney-local-health-district
#4
P N Ding, T L Roberts, W Chua, T M Becker, J Descallar, P Y Yip, V J Bray
AIMS: We aim to describe clinical characteristics, treatment patterns and factors influencing outcomes in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in SWSLHD. METHODS: Retrospective review of patients with EGFR-mutated NSCLC diagnosed between January 2010 and June 2016. RESULTS: A total of 85 EGFR-mutated NSCLC patients were identified; 80 (94%) received first line treatment with EGFR-TKI. The median follow-up was 10.7 months with a median duration of treatment of 9 months...
July 25, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28742266/p-coumaric-acid-a-dietary-polyphenol-ameliorates-inflammation-and-curtails-cartilage-and-bone-erosion-in-the-rheumatoid-arthritis-rat-model
#5
Manoj Kumar Neog, Samuel Joshua Pragasam, Moorthy Krishnan, Mahaboobkhan Rasool
This study was designed to explore the underlying mechanism of p-coumaric acid (CA), a dietary polyphenol in adjuvant-induced arthritis (AIA) rat model with reference to synovitis and osteoclastogenesis. Celecoxib (COX-2 selective inhibitor) (5 mg/kg b.wt) was used as a reference drug. CA remarkably suppressed the paw edema, body weight loss and inflammatory cytokine and chemokine levels (TNF-α, IL-1β, IL-6, and MCP-1) in serum and ankle joint of arthritic rats. Consistently, CA reduced the expression of osteoclastogenic factors (RANKL and TRAP), pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), and inflammatory enzymes (iNOS and COX-2) in arthritic rats...
July 25, 2017: BioFactors
https://www.readbyqxmd.com/read/28740516/pge2-promotes-the-migration-of-mesenchymal-stem-cells-through-the-activation-of-fak-and-erk1-2-pathway
#6
Xiaomin Lu, Jibin Han, Xiuping Xu, Jingyuan Xu, Ling Liu, Yingzi Huang, Yi Yang, Haibo Qiu
A critical step of MSCs therapy is dependent on its ability to migrate into the sites of injury, so various approaches have been introduced to boost the migratory ability of MSCs. PGE2 is the major prostaglandin generated by COX enzymes and has been implicated in inflammatory response. Evidence indicates that PGE2 can facilitate MSCs migration. Further exploration of the underlying molecular mechanism participating in the promigratory ability of PGE2 may provide a novel strategy to improve MSC transplantation efficacy...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28739304/role-of-nadphox-rho-kinase-signaling-in-the-cyclosporine-nsaids-interactions-on-blood-pressure-and-baroreflexes-in-female-rats
#7
Hanan M El-Gowelli, Karim S Ibrahim, Ahmed F El-Yazbi, Mahmoud M El-Mas
AIMS: The hypertensive effect of the immunosuppressant drug cyclosporine (CSA) is paralleled, and probably triggered, by impaired arterial baroreceptor sensitivity (BRS). Here we asked if these effects of CSA are influenced by co-administration of nonsteroidal antiinflammatory drugs (NSAIDs) and if the oxidative NADPH-oxidase (NADPHox)/Rho-kinase (ROCK) pathway mediates this interaction. MATERIALS AND METHODS: Female rats were treated for 10days with CSA (25mg/kg/day), diclofenac (DIC, COX-1/COX-2 inhibitor, 1mg/kg/day), celecoxib (COX-2 inhibitor, 10mg/kg/day), or their combinations...
July 21, 2017: Life Sciences
https://www.readbyqxmd.com/read/28738499/aqueous-extract-of-codium-fragile-suppressed-inflammatory-responses-in-lipopolysaccharide-stimulated-raw264-7-cells-and-carrageenan-induced-rats
#8
Seul Ah Lee, Sung-Min Moon, Yun Hee Choi, Seul Hee Han, Bo-Ram Park, Mi Suk Choi, Jae-Sung Kim, Yong Hwan Kim, Do Kyung Kim, Chun Sung Kim
Codium fragile (Suringar) Hariot has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria and has been shown to have various biological effects. In this study, we evaluated the anti-inflammatory effects of aqueous extract of C. fragile (AECF) using in vitro and in vivo models. Nitric oxide (NO), prostaglandin E2 (PGE2), inflammatory-related mRNAs, and proteins were determined using the Griess assay, enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), and western blotting, respectively...
July 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28738385/pharmacological-and-nonpharmacological-interventions-to-arrest-neuroprogression-in-psychiatric-disorders
#9
Fotini Boufidou, Angelos Halaris
The concept of neuroprogression describes the progressive course of the disorder and stresses the progressive, recurrent, and chronic course of the disease entity under consideration. It subsumes clinical manifestations of the disease process and may also entail morphological, biochemical, neurochemical, immunological, physiological, and genetic aspects that contribute to the progressive course of the disease in question. In an attempt to identify the appropriate agent or method that could arrest neuroprogression in psychiatric patients, we conducted an evaluation of the use of anti-inflammatory drugs under the perspective of current pharmacological and neurophysiological data...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28738249/new-1-3-4-oxadiazole-oxime-hybrids-design-synthesis-anti-inflammatory-cox-inhibitory-activities-and-ulcerogenic-liability
#10
Heba S Abd-Ellah, Mohamed Abdel-Aziz, Mai E Shoman, Eman A M Beshr, TamerS Kaoud, Al-Shaimaa F F Ahmed
A series of new 1,3,4-oxadiazole/oxime hybrids were synthesized and designed as potent COX inhibitors. The prepared compounds were evaluated for their anti-inflammatory, antioxidant and ulcerogenic activities. The results indicated that the prepared compounds exhibited remarkable anti-inflammatory activity with (69.60-109.60% of indomethacin activity) after 4h. In vitro COX inhibitory assay showed that compounds 6d and 7h are potent COX inhibitors with IC50 of (1.10-0.94) and (2.30-5.00) µM on both COX-1 and COX-2 respectively...
June 15, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28737121/the-impact-of-cancer-development-on-the-risk-of-mycobacterial-diseases-among-rheumatoid-arthritis-patients
#11
S-W Pan, Y-F Yen, Y R Kou, P-H Chuang, J-Y Feng, Y-J Chan, W-J Su
Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free)...
July 24, 2017: Epidemiology and Infection
https://www.readbyqxmd.com/read/28733349/constitutive-ido1-expression-in-human-tumors-is-driven-by-cyclooxygenase-2-and-mediates-intrinsic-immune-resistance
#12
Marc Hennequart, Luc Pilotte, Stefania Cane, Delia Hoffmann, Vincent Stroobant, Etienne De Plaen, Benoît J Van den Eynde
Tumors use various mechanisms to avoid immune destruction. Cyclooxygenase-2 (COX-2) expression may be a driver of immune suppression in melanoma, but the mechanisms involved remain elusive. Here, we show that COX-2 expression drives constitutive expression of indoleamine 2,3-dioxygenase 1 (IDO1) in human tumor cells. IDO1 is an immunosuppressive enzyme that degrades tryptophan. In a series of seven human tumor lines, constitutive IDO1 expression depends on COX-2 and prostaglandin E2 (PGE2), which, upon autocrine signaling through the EP receptor, activates IDO1 via the PKC and PI3K pathways...
July 21, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28722207/antihypertensive-drug-associated-angioedema-effect-modification-by-race-ethnicity
#13
Marsha E Reichman, Michael Wernecke, David J Graham, Jiemin Liao, John Yap, Yoganand Chillarige, Mary Ross Southworth, Stephine Keeton, Margie R Goulding, Katrina Mott, Jeffrey A Kelman
PURPOSE: Assess angioedema risk with exposure to angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) compared with beta-blockers, by race/ethnicity. METHODS: New-user cohorts of Medicare beneficiaries 65 years or older initiating ACEI, ARB, or beta-blocker treatment from March 2007 to March 2014 were constructed. Angioedema incidence rates by drug and race/ethnicity were computed for 1-30 and 31-365 days of treatment. Cox proportional hazards regression was used to examine angioedema risk between cohorts...
July 19, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28720504/synthesis-of-novel-hybrids-of-pyrazole-and-coumarin-as-dual-inhibitors-of-cox-2-and-5-lox
#14
Fa-Qian Shen, Zhong-Chang Wang, Song-Yu Wu, Shen-Zhen Ren, Ruo-Jun Man, Bao-Zhong Wang, Hai-Liang Zhu
In our previous study, we designed a series of pyrazole derivatives as novel COX-2 inhibitors. In order to obtain novel dual inhibitors of COX-2 and 5-LOX, herein we designed and synthesized 20 compounds by hybridizing pyrazole with substituted coumarin who was reported to exhibit 5-LOX inhibition to select potent compounds using adequate biological trials sequentially including selective inhibition of COX-2 and 5-LOX, anti-proliferation in vitro, cells apoptosis and cell cycle. Among them, the most potent compound 11g (IC50=0...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28719356/co-incubation-of-pmn-and-caco-2-cells-modulates-inflammatory-potential
#15
M B Schaefer, C A Schaefer, M Hecker, R E Morty, M Witzenrath, W Seeger, K Mayer
Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28718447/prostaglandin-e2-signaling-alternative-target-for-glioblastoma
#16
Jianxiong Jiang, Jiange Qiu, Qianqian Li, Zhi Shi
Elevated cyclooxygenase-2 (COX-2) and the associated inflammation within the brain contribute to glioblastoma development. However, medical use of COX inhibitors in glioblastoma treatment has been limited due to their well-documented vascular toxicity and inconsistent outcomes from recent human studies. Prostaglandin E2 (PGE2) has emerged as a principal mediator for COX-2 cascade-driven gliomagenesis. Are PGE2 terminal synthases and receptors feasible therapeutic targets for glioblastoma?
February 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28715344/community-acquired-pneumonia-incidence-before-and-after-proton-pump-inhibitor-prescription-population-based-study
#17
Fatmah Othman, Colin J Crooks, Timothy R Card
Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association.Design Cohort study and self controlled case series.Setting Clinical Practice Research Datalink (1990 to 2013) in UK.Participants Adult patients with a new prescription for a PPI individually matched with controls.Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription...
November 15, 2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28712765/losartan-reverses-cox-2-dependent-vascular-dysfunction-in-offspring-of-hyperglycaemic-rats
#18
Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements...
July 13, 2017: Life Sciences
https://www.readbyqxmd.com/read/28711545/antiulcer-properties-of-fruits-and-vegetables-a-mechanism-based-perspective
#19
REVIEW
Choudhary Harsha, Kishore Banik, Devivasha Bordoloi, Ajaikumar B Kunnumakkara
Gastric ulcer is the damage caused to mucosal layer of the stomach under the action of various factors like high levels of acid and pepsin, invasion by Helicobacter pylori, etc. Although most cases have been controlled and the rate of ulcer occurrence has reduced over the last few decades, gastric ulcer still holds a prime concern today. A range of palliative medicines comprising proton pump inhibitors, H2 receptor antagonists, COX-2 inhibitors (coxibs) is widely in use and patients have also been administered with acid suppression therapies...
July 12, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28711084/herpes-zoster-in-psoriasis-patients-treated-with-tofacitinib
#20
Kevin L Winthrop, Mark Lebwohl, Arnon D Cohen, Jeffrey M Weinberg, Stephen K Tyring, Scott T Rottinghaus, Pankaj Gupta, Kaori Ito, Huaming Tan, Mandeep Kaur, Alexander Egeberg, Lotus Mallbris, Hernan Valdez
BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models...
August 2017: Journal of the American Academy of Dermatology
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