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https://www.readbyqxmd.com/read/28535469/novel-propanamides-as-fatty-acid-amide-hydrolase-inhibitors
#1
Alessandro Deplano, Carmine Marco Morgillo, Monica Demurtas, Emmelie Björklund, Mariateresa Cipriano, Mona Svensson, Sanaz Hashemian, Giovanni Smaldone, Emilia Pedone, F Javier Luque, Maria G Cabiddu, Ettore Novellino, Christopher J Fowler, Bruno Catalanotti, Valentina Onnis
Fatty acid amide hydrolase (FAAH) has a key role in the control of the cannabinoid signaling, through the hydrolysis of the endocannabinoids anandamide and in some tissues 2-arachidonoylglycerol. FAAH inhibition represents a promising strategy to activate the cannabinoid system, since it does not result in the psychotropic and peripheral side effects characterizing the agonists of the cannabinoid receptors. Here we present the discovery of a novel class of profen derivatives, the N-(heteroaryl)-2-(4-((2-(trifluoromethyl)pyridin-4-yl)amino)phenyl)propanamides, as FAAH inhibitors...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28534978/demethylzeylasteral-ameliorates-inflammation-in-a-rat-model-of-unilateral-ureteral-obstruction-through-inhibiting-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-pathway
#2
Qiang Wang, Yanmei Xiao, Tongwei Liu, Haibo Yuan, Chunwu Li
The present study investigated the pharmacodynamic role and therapeutic mechanism of demethylzeylasteral in the suppression of inflammation in a rat model of unilateral ureteral obstruction and reduction in nuclear factor (NF)‑κB pathway activity. The rats in the unilateral ureteral obstruction model were treated with 30‑120 mg/kg demethylzeylasteral for 8 weeks. The activities of tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and caspase‑3/9, and the protein expression levels of cyclooxygenase (COX)‑2 and intercellular adhesion molecule‑1 (ICAM‑1) and NF‑κB p65 were analyzed using ELISA kits and western blot analyses, respectively...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28533319/evaluating-the-cardiovascular-safety-of-nonsteroidal-anti-inflammatory-drugs
#3
REVIEW
Elliott M Antman
Some drugs used to treat noncardiovascular conditions may adversely impact the cardiovascular status of individuals both with and without known cardiovascular disease. When the US Food and Drug Administration judges the potential cardiovascular safety signal to be of sufficient concern, it may require the pharmaceutical manufacturer of the drug in question to conduct a postmarketing (phase 4) randomized controlled trial (RCT). Although historically many phase 4 RCTs focused on efficacy (using a superiority design), contemporary phase 4 RCTs often are focused on safety and use a noninferiority design...
May 23, 2017: Circulation
https://www.readbyqxmd.com/read/28532683/the-essential-oil-from-the-twigs-of-cinnamomum-cassia-presl-inhibits-oxytocin-induced-uterine-contraction-in-vitro-and-in-vivo
#4
Lan Sun, Li-Na Liu, Jia-Chun Li, Yao-Zhong Lv, Shao-Bo Zong, Jun Zhou, Zheng-Zhong Wang, Jun-Ping Kou, Wei Xiao
ETHNOPHARMACOLOGICAL RELEVANCE: The twigs and bark of Cinnamomum cassia Presl (Lauraceae) are widely used in traditional Chinese medicine in the treatment of tumor, abdominal pain, dysmenorrhea, digestive system disease and inflammatory diseases. The aim of this study was to determine the inhibitory effect of the essential oil from the twigs of Cinnamomum cassia Presl (EOCC) on uterine contraction in vitro and in vivo. MATERIALS AND METHODS: The Institute of Cancer Research (ICR) mouse uterine contraction was induced by oxytocin (OT) exposure following estradiol benzoate pretreatment...
May 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28530811/multi-targeted-imidazoles-potential-therapeutic-leads-for-alzheimer-s-and-other-neurodegenerative-diseases
#5
Anne-Sophie Cornec, Ludovica Monti, Jane Kovalevich, Vishruti Makani, Michael J James, Krishna G Vijayendran, Killian Oukoloff, Yuemang Yao, Virginia M-Y Lee, John Q Trojanowski, Amos B Smith Iii, Kurt R Brunden, Carlo Ballatore
Alzheimer's disease (AD) is a complex, multifactorial disease in which different neuropathological mechanisms are likely involved, including those associated with pathological tau and Aβ species, as well as neuroinflammation. In this context, the development of single multi-targeted therapeutics directed against two or more disease mechanisms could be advantageous. Starting from a series of 1,5-diarylimidazoles with microtubule (MT)-stabilizing activity and structural similarities with known NSAIDs, we conducted structure-activity relationship studies that led to the identification of multi-targeted prototypes with activities as MT-stabilizing agents and/or inhibitors of the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28530128/in-vivo-endocrine-secretion-of-prostacyclin-following-expression-of-a-cox-1-pgis-fusion-protein-in-the-salivary-glands-of-rats-via-non-viral-gene-therapy
#6
Zhimin Wang, Raymond L Benza, Lee Zourelias, Angela Sanguino, Ramaz Geguchadze, Kelly J Shields, Changgong Wu, Kristin B Highland, Michael J Passineau
Pulmonary arterial hypertension is a progressive disease that culminates in right heart failure and death. Prostacyclin(PGI2) and its derivatives are effective treatments for PAH when administered as continuous parenteral infusions. This treatment paradigm requires medical sophistication, and patients are at risk for complications from an indewelling catheter; drug interruptions may result in rebound pulmonary hypertension and death. We hypothesized that the salivary gland can be repurposed into an endogenous production site for circulating PGI2 through the expression of a fusion protein embodying cyclooxygenase-1(Cox1) and prostacyclin synthase(PGIS) domains...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28529269/possible-role-of-ppar%C3%AE-in-the-negative-regulation-of-ovulatory-cascade-and-luteal-development-in-rats
#7
Ryohei Funahashi, Takanobu Sakamoto, Norihito Taguchi, Ryosuke Naiki, Ryota Terashima, Mitsumori Kawaminami, Shiro Kurusu
Peroxisome proliferator-activated receptor γ (PPARγ), a member of a nuclear receptor family, has been shown to be implicated in various reproductive processes. Here, we evaluated possible roles of PPARγ in ovulation and luteal development in a gonadotropins-primed immature rat model. Immunoreactive PPARγ was expressed in granulosa cells of eCG-stimulated mature follicles, and its expression level decreased following ovulatory hCG stimulus. Intra-bursal treatment with rosiglitazone (a PPARγ agonist) simultaneously with subcutaneously administered hCG blocked the induction of cyclooxygenase-2 and steroidogenic acute regulatory protein (StAR) in preovulatory follicles...
May 19, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28529178/anti-inflammatory-activities-of-compounds-from-twigs-of-morus-alba
#8
Huynh Nguyen Khanh Tran, Van Thu Nguyen, Jeong Ah Kim, Seong Soo Rho, Mi Hee Woo, Jae Sui Choi, Jeong-Hyung Lee, Byung Sun Min
Five new compounds, 10-oxomornigrol F (1), (7″R)-(-)-6-(7″-hydroxy-3″,8″-dimethyl-2″,8″-octadien-1″-yl)apigenin (2), ramumorin A (3), ramumorin B (4), and (4S,7S,8R)-trihydroxyoctadeca-5Z-enoic acid (5), together with 31 known compounds (6-36), were isolated from the twigs of Morus alba (Moraceae). The chemical structures of these compounds were established using spectroscopic analyses, 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and Mosher's methods. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW 264...
May 18, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28528513/the-expansive-role-of-oxylipins-on-platelet-biology
#9
REVIEW
Jennifer Yeung, Megan Hawley, Michael Holinstat
In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators (oxylipins) from polyunsaturated fatty acids (PUFAs) which exhibit pro- or anti-thrombotic activity. Over the years, novel oxylipins generated from the interplay of theoxygenase activity in various cells, such as the specialized pro-resolving mediators (SPMs), have been identified and investigated in inflammatory disease models. Although platelets have been implicated in inflammation, the role and mechanism of these SPMs produced from immune cells on platelet function are still unclear...
May 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28528506/exposure-of-marine-mussels-to-diclofenac-modulation-of-prostaglandin-biosynthesis
#10
Frédérique Courant, Lauren Arpin-Pont, Bénilde Bonnefille, Sébastien Vacher, Marina Picot-Groz, Elena Gomez, Hélène Fenet
Human pharmaceuticals, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are an emerging threat to marine organisms. NSAIDs act through inhibition of cyclooxygenase (COX) conversion of arachidonic acid into prostaglandins. One experiment was carried out whereby marine mussels were exposed for 72 h to 1 and 100 μg/L diclofenac (DCF). A specific and sensitive method using liquid chromatography high-resolution tandem mass spectrometry was developed to quantify DCF in mussel tissues. The developed method could also clearly identify and quantify COX products, i...
May 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28528242/efficacy-and-safety-of-celecoxib-monotherapy-for-mild-to-moderate-depression-in-patients-with-colorectal-cancer-a-randomized-double-blind-placebo-controlled-trial
#11
Maryam Alamdarsaravi, Alireza Ghajar, Ahmad-Ali Noorbala, Mohammad Arbabi, Amirhossein Emami, Farhad Shahei, Mehrzad Mirzania, Morteza Jafarinia, Mohsen Afarideh, Shahin Akhondzadeh
Cancer-related inflammation is an essential process in malignancies. Celecoxib, a nonsteroidal anti-inflammatory drug that acts via the selective inhibition of cyclooxygenase (COX)-2, has shown favorable effects in several psychiatric disorders. The present study aimed to assess the safety and efficacy of celecoxib single therapy on depressive symptoms of patients with colorectal cancer who underwent chemotherapy. The study was conducted as a 6-week, parallel-group, randomized, double-blind, placebo-controlled trial...
May 17, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28526927/sodium-thiosulphate-attenuates-brain-inflammation-induced-by-systemic-lipopolysaccharide-administration-in-c57bl-6j-mice
#12
Gonzalo Acero, Miryam Nava Catorce, Ricardo González-Mendoza, Marco Antonio Meraz-Rodríguez, Luis Fernando Hernández-Zimbron, Roberto González-Salinas, Goar Gevorkian
It has been demonstrated that peripheral infections accompanied by neuroinflammation may modify brain development or affect normal brain aging and represent major risk factors for the development of neurological disorders. A wide range of synthetic and natural compounds with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated for the first time that sodium thiosulphate (STS), a known antidote approved for treatment of certain medical conditions, is capable of reducing brain inflammation caused by systemic LPS administration...
May 19, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28526157/pharmacology-of-acetaminophen-nonsteroidal-antiinflammatory-drugs-and-steroid-medications-implications-for-anesthesia-or-unique-associated-risks
#13
REVIEW
Kenneth D Candido, Oscar J Perozo, Nebojsa Nick Knezevic
Acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), and corticosteroids, historically used in perioperative management, are potent analgesic medications. They primarily inhibit the cyclooxygenase (COX) enzyme, decreasing the synthesis of prostaglandins, and modulating pain and temperature. Acetaminophen does not inhibit this synthesis at the inflammatory site. The primary mechanism of action of corticosteroids involves regulation of nuclear expression of genes involved in inflammatory pathways and other systemic effects...
June 2017: Anesthesiology Clinics
https://www.readbyqxmd.com/read/28525367/liposomal-co-delivered-oleanolic-acid-attenuates-doxorubicin-induced-multi-organ-toxicity-in-hepatocellular-carcinoma
#14
Muhammad Sarfraz, Attia Afzal, Shahid Masood Raza, Sajid Bashir, Asadullah Madni, Muhammad Waseem Khan, Xiang Ma, Guangya Xiang
Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC)...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524628/myenteric-neuroprotective-role-of-aspirin-in-acute-and-chronic-experimental-infections-with-trypanosoma-cruzi
#15
J Y Oda, M O Belém, T M Carlos, R Gouveia, B F C Luchetti, N M Moreira, C L Massocatto, S M Araújo, D M G Sant Ana, N C Buttow, P Pinge-Filho, E J A Araújo
BACKGROUND: Experimental and clinical studies have shown that myenteric neuron cell death during infection with Trypanosoma cruzi mainly occurs in the esophagus and colon, resulting in megaesophagus and megacolon, respectively. Evidence suggests that the cyclooxygenase enzyme (COX) is involved in the T. cruzi invasion process. The use of low-dose aspirin (ASA), a COX-1/COX-2 inhibitor, has been shown to reduce infection with T. cruzi. Therefore, in this study, we evaluated the effects of treatment with low-dose ASA on myenteric colonic neurons during murine infection with T...
May 19, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28524086/dietary-green-pea-protects-against-dss-induced-colitis-in-mice-challenged-with-high-fat-diet
#16
Shima Bibi, Luís Fernando de Sousa Moraes, Noelle Lebow, Mei-Jun Zhu
Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2...
May 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28524081/protective-effects-of-tormentic-acid-a-major-component-of-suspension-cultures-of-eriobotrya-japonica-cells-on-acetaminophen-induced-hepatotoxicity-in-mice
#17
Wen-Ping Jiang, Shyh-Shyun Huang, Yoshikazu Matsuda, Hiroshi Saito, Naoto Uramaru, Hui-Ya Ho, Jin-Bin Wu, Guan-Jhong Huang
An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues...
May 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#18
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28522946/parthenolide-promotes-apoptotic-cell-death-and-inhibits-the-migration-and-invasion-of-sw620-cells
#19
Yu Chuan Liu, Se Lim Kim, Young Ran Park, Soo-Teik Lee, Sang Wook Kim
BACKGROUND/AIMS: Parthenolide (PT), a principle component derived from feverfew (Tanacetum parthenium), is a promising anticancer agent and has been shown to promote apoptotic cell death in various cancer cells. In this study, we focused on its functional role in apoptosis, migration, and invasion of human colorectal cancer (CRC) cells. METHODS: SW620 cells were employed as representative human CRC cells. We performed the MTT assay and cell cycle analysis to measure apoptotic cell death...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28522759/effect-of-cyclooxygenase-inhibition-on-the-inspiratory-muscle-metaboreflex-induced-cardiovascular-consequences-in-men
#20
Joshua R Smith, Kaylin D Didier, Shane M Hammer, Andrew M Alexander, Stephanie P Kurti, Steven W Copp, Thomas J Barstow, Craig A Harms
Inspiratory muscle metaboreflex activation increases mean arterial pressure (MAP) and limb vascular resistance (LVR) and decreases limb blood flow (Q̇L). Cyclooxygenase (COX) inhibition has been found to attenuate limb skeletal muscle metaboreflex-induced increases in muscle sympathetic nerve activity. We hypothesized that compared to placebo (PLA), COX inhibition would attenuate inspiratory muscle metaboreflex-induced 1) increases in MAP and LVR and 2) decreases in Q̇L Seven men (22±1 years) were recruited and orally consumed ibuprofen (IB, 10mg/kg) or PLA 90 min prior to performing the cold pressor test (CPT) for 2 min and inspiratory resistive breathing task (IRBT) for 14...
May 18, 2017: Journal of Applied Physiology
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