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https://www.readbyqxmd.com/read/29475100/new-thiazolidinedione-lpsf-gq-2-inhibits-nf%C3%AE%C2%BAb-and-mapk-activation-in-lps-induced-acute-lung-inflammation
#1
Laise Aline Martins Dos Santos, Gabriel Barros Rodrigues, Fernanda Virgínia Barreto Mota, Maria Eduarda Rocha de França, Karla Patrícia de Souza Barbosa, Wilma Helena de Oliveira, Sura Wanessa Santos Rocha, Deniele Bezerra Lós, Amanda Karolina Soares Silva, Teresinha Gonçalves da Silva, Christina Alves Peixoto
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are responsible for high mortality rates in critical patients. Despite >50 years of intensive research, there is no pharmacologically effective treatment to treat ALI. PPARs agonists, chemically named thiazolidinediones (TZDs) have emerged as potential drugs for the treatment of ALI and ARDS due to their anti-inflammatory efficacy. The present study aims to evaluate the potential anti-inflammatory effects of new TZDs derivatives, LPSF/GQ-2 and LPSF/RA-4, on ALI induced by LPS...
February 20, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29475097/kaempferol-3-o-%C3%AE-d-glucuronate-exhibit-potential-anti-inflammatory-effect-in-lps-stimulated-raw-264-7-cells-and-mice-model
#2
Vidushi Khajuria, Shilpa Gupta, Neha Sharma, Harshita Tiwari, Subhash Bhardwaj, Prabhu Dutt, Naresh Satti, Amit Nargotra, Asha Bhagat, Zabeer Ahmed
Kaempferol-3-O-β-d-glucuronide (K3G) having various pharmacological effects was explored for its anti-inflammatory effect in LPS induced RAW 264.7 cells and mice model. K3G significantly inhibited various pro-inflammatory mediators like IL-1β, NO, PGE2, and LTB4. It upregulated the secretion of anti-inflammatory cytokine IL-10. K3G is found to reduce inflammation when studied for parameters like phagocytic index, carrageenan induced paw edema in mice and organ weight. It reduced inflammation in a dose dependent manner both in-vitro and in-vivo...
February 20, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29475061/a-fungal-metabolite-zearalenone-as-a-cftr-inhibitor-and-potential-therapy-of-secretory-diarrheas
#3
Paradorn Muangnil, Saravut Satitsri, Kwanruthai Tadpetch, Patchreenart Saparpakorn, Varanuj Chatsudthipong, Supa Hannongbua, Vatcharin Rukachaisirikul, Chatchai Muanprasat
Overstimulation of CFTR-mediated Cl- secretion plays an important role in the pathogenesis of secretory diarrheas, which remain an important global health problem. This study aimed to identify inhibitors of CFTR-mediated Cl- secretion from a library of fungus-derived compounds and to evaluate their pharmacological properties and anti-diarrheal utility. We identified zearalenone, 7'-dehydrozearalenone and 8'-hydroxyzearalenone isolated from the seagrass-derived fungus Fusarium sp. PSU-ES123 as inhibitors of CFTR-mediated Cl- secretion in human intestinal epithelial (T84) cells...
February 20, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29474893/better-airway-resistance-reduction-profile-in-intubated-copd-patients-by-personalized-bronchodilator-dosing-a-pilot-randomized-control-trial
#4
Shin-Hwar Wu, Lih-Jen Shyu, Chin-Hsing Li, Chao-Hung Yu, Huang-Chi Chen, Chew-Teng Kor, Chu-Hsien Wang, Kai-Huang Lin
INTRODUCTION: The optimal dose of inhaled metered-dose bronchodilators for intubated patients with chronic obstructive pulmonary disease (COPD) is unknown. In this study, we proposed a bronchodilator dosing schedule based on an individual's airway resistance (Raw ) and tested its efficacy in reducing Raw . METHODS: A total of 51 newly admitted patients with invasively ventilated COPD were randomly assigned to receive personalized or fixed bronchodilator dosing. Personal target Raw was defined by measuring each individual's Raw after maximal pharmacologic bronchodilatation...
February 20, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29474891/regulation-of-kv7-2-kv7-3-channels-by-cholesterol-relevance-of-an-optimum-plasma-membrane-cholesterol-content
#5
Mayra Delgado-Ramírez, Sergio Sánchez-Armass, Ulises Meza, Aldo A Rodríguez-Menchaca
Kv7.2/Kv7.3 channels are the molecular correlate of the M-current, which stabilizes the membrane potential and controls neuronal excitability. Previous studies have shown the relevance of plasma membrane lipids on both M-currents and Kv7.2/Kv7.3 channels. Here, we report the sensitive modulation of Kv7.2/Kv7.3 channels by membrane cholesterol level. Kv7.2/Kv7.3 channels transiently expressed in HEK-293 cells were significantly inhibited by decreasing the cholesterol level in the plasma membrane by three different pharmacological strategies: methyl-β-cyclodextrin (MβCD), Filipin III, and cholesterol oxidase treatment...
February 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29474877/the-grp78-bip-inhibitor-ha15-synergizes-with-mitotane-action-against-adrenocortical-carcinoma-cells-through-convergent-activation-of-er-stress-pathways
#6
Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Cyril Ronco, Rachid Benhida, Stéphane Rocchi, Enzo Lalli
Many types of cancer cells present constitutively activated ER stress pathways because of their significant burden of misfolded proteins coded by mutated and rearranged genes. Further increase of ER stress by pharmacological intervention may shift the balance towards cell death and can be exploited therapeutically. Recent studies have shown that an important component in the mechanism of action of mitotane, the only approved drug for the medical treatment of adrenocortical carcinoma (ACC), is represented by activation of ER stress through inhibition of the SOAT1 enzyme and accumulation of toxic lipids...
February 20, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29474499/risk-factors-control-for-primary-prevention-of-cardiovascular-disease-in-men-evidence-from-the-aragon-workers-health-study-awhs
#7
Isabel Aguilar-Palacio, Sara Malo, Cristina Feja, MªJesús Lallana, Montserrat León-Latre, José Antonio Casasnovas, MªJosé Rabanaque, Eliseo Guallar
Benefits of cardiovascular disease (CVD) risk factors control are well known, but goals achievement remains low. The objective of this study is to evaluate the prevalence of CVD risk factors among men ina worker's cohort with no previous CVD, to study control variations across time and the factors associated with poor control. To this end, we conducted a cohort reexamination (2010-2014) within the context of the Aragon Workers Health Study (AWHS). Data from working characteristics, analytical values and pharmacological prescription were included in the analysis...
2018: PloS One
https://www.readbyqxmd.com/read/29474466/preclinical-pharmacology-of-azd9977-a-novel-mineralocorticoid-receptor-modulator-separating-organ-protection-from-effects-on-electrolyte-excretion
#8
Krister Bamberg, Ulrika Johansson, Karl Edman, Lena William-Olsson, Susanna Myhre, Anders Gunnarsson, Stefan Geschwindner, Anna Aagaard, Anna Björnson Granqvist, Frédéric Jaisser, Yufeng Huang, Kenneth L Granberg, Rasmus Jansson-Löfmark, Judith Hartleib-Geschwindner
Excess mineralocorticoid receptor (MR) activation promotes target organ dysfunction, vascular injury and fibrosis. MR antagonists like eplerenone are used for treating heart failure, but their use is limited due to the compound class-inherent hyperkalemia risk. Here we present evidence that AZD9977, a first-in-class MR modulator shows cardio-renal protection despite a mechanism-based reduced liability to cause hyperkalemia. AZD9977 in vitro potency and binding mode to MR were characterized using reporter gene, binding, cofactor recruitment assays and X-ray crystallopgraphy...
2018: PloS One
https://www.readbyqxmd.com/read/29474345/opioid-related-genetic-polymorphisms-do-not-influence-postoperative-opioid-requirement-a-prospective-observational-study
#9
Frédéric Aubrun, Noël Zahr, Olivier Langeron, Nicolas Boccheciampe, Nathalie Cozic, Lisa Belin, Jean-Sebastien Hulot, Frederic Khiami, Bruno Riou
BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics...
February 22, 2018: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/29474155/a-multiplexed-mass-spectrometry-based-assay-for-robust-quantification-of-phosphosignaling-in-response-to-dna-damage
#10
Jeffrey R Whiteaker, Lei Zhao, Rick Saul, Jan A Kaczmarczyk, Regine M Schoenherr, Heather D Moore, Corey Jones-Weinert, Richard G Ivey, Chenwei Lin, Tara Hiltke, Kerryn W Reding, Gordon Whiteley, Pei Wang, Amanda G Paulovich
A lack of analytically robust and multiplexed assays has hampered studies of the large, branched phosphosignaling network responsive to DNA damage. To address this need, we developed and fully analytically characterized a 62-plex assay quantifying protein expression and post-translational modification (phosphorylation and ubiquitination) after induction of DNA damage. The linear range was over 3 orders of magnitude, the median inter-assay variability was 10% CV and the vast majority (∼85%) of assays were stable after extended storage...
February 23, 2018: Radiation Research
https://www.readbyqxmd.com/read/29473944/non-endocannabinoid-n-acylethanolamines-and-2-monoacylglycerols-in-the-intestine
#11
REVIEW
Harald S Hansen, Vasiliki Vana
This review focuses on recent findings of the physiological and pharmacological role of non-endocannabinoid NAEs and 2-MAGs in the intestine and their involvement in the gut-brain signaling. Dietary fat suppress food intake and much research concerns the known gut peptides e.g. GLP-1, and CCK. NAEs and 2-MAGs represent another class of local gut signals most probably involved in the regulation of food intake. We discuss the putative biosynthetic pathways and targets of NAEs in the intestine as well as their anorectic role and changes in intestinal levels depending on the nutritional status...
February 23, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29473719/diabetic-macular-edema-current-understanding-pharmacologic-treatment-options-and-developing-therapies
#12
Kevin Miller, Jorge A Fortun
Diabetic retinopathy and diabetic macular edema comprise a major source of visual disability throughout the developed world. The etiology and pathogenesis of macular edema is intricate and multifactorial, in which the hyperglycemic state in diabetes induces a microangiopathy. Through several inflammatory and vasogenic mediators, including vascular endothelial growth factor (VEGF) upregulation and inflammatory cytokines and chemokines, pathologic changes are induced in the vascular endothelium triggering breakdown of the blood retinal barrier, causing extravasation of fluid into the extracellular space and manifesting clinically as macular edema, resulting in visual loss...
January 2018: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/29473532/the-promising-pharmacological-effects-and-therapeutic-medicinal-applications-of-punica-granatum-l-pomegranate-as-a-functional-food-in-humans-and-animals
#13
Kuldeep Dhama
BACKGROUND: Punica granatum L (pomegranate), is a shrub mostly available in the Mediterranean Sea region. The fruits have gained the substantial attention among researchers due to its promising biological activities including anti-inflammatory, antibacterial, antidiarrheal, immune modulatory, antitumor, wound healing and antifungal that have been attributed to various constituents of seeds, bark, juice, pericarp and leaf of this tree across the globe. The phenolic compounds of pomegranate have been documented to possess numbers of prophylactic and therapeutic utilities against various pathological infections as well as non-infectious disorders...
February 21, 2018: Recent Patents on Inflammation & Allergy Drug Discovery
https://www.readbyqxmd.com/read/29473524/pharmacogenetics-of-glucagon-like-peptide-1-agonists-for-the-treatment-of-type-2-diabetes-mellitus
#14
Spyridon Karras, Eleni Rapti, Theocharis Koufakis, Angeliki Kyriazou, Dimitrios Goulis, Kalliopi Kotsa
BACKGROUND: Pharmacogenetics is a promising area of medical research, providing methods to identify the appropriate pharmaceutical agent and dosing for each unique patient. Glucagon-like peptide-1 (GLP-1) agonists are a novel therapeutic choice used in the treatment of type 2 diabetes mellitus (T2DM), demonstrating efficacy regarding glycemic control and weight loss. Therapeutic response to GLP-1 agonist treatment is a complex biophenomenon, dependent on a plethora of modifiable (diet, exercise, adherence) and non-modifiable (genetic individual variants, ethnic characteristics) parameters...
February 21, 2018: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/29473499/natural-aristolochia-alkaloid-aristololactam-%C3%AE-d-glucoside-interaction-with-biomacromolecules-and-correlation-to-the-biological-perspectives
#15
Abhi Das, Gopinatha Suresh Kumar
Backgound: Natural aristolochia alkaloids have attracted the attention of both chemists and biologists from the stand point of their structural and pharmacological aspects. Many of the compounds isolated in this group are potent tumor inhibitors. These are divided into nitrophenanthrinic acid, phenanthrene lactams and isoquinoline alkaloids. A number of structure-activity studies have been performed on aristolochia alkaloids. Of particular interest is the molecule with the β-D-glucoside moiety that has similarity to the clinical anticancer agent daunomycin...
February 22, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29472860/magnesium-lithospermate-b-protects-against-lipopolysaccharide-induced-bone-loss-by-inhibiting-rankl-rank-pathway
#16
Jihai Wang, Xuejian Wu, Yongzhuang Duan
Lipopolysaccharide (LPS) can induce bone loss by stimulating bone resorption. Natural compounds have great potential for the treatment of osteolytic bone diseases. Magnesium lithospermate B (MLB) plays an important role in protecting against oxidative damage and also has potential anti-inflammatory pharmacological properties. However, its role in LPS-induced bone loss is still unknown. In the present study, we observed the effects of MLB on LPS-induced bone damage and investigated the possible mechanisms. The bone loss models were established by LPS administration in male Sprague-Dawley rats...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29472858/an-integrated-lipidomics-and-phenotype-study-reveals-protective-effect-and-biochemical-mechanism-of-traditionally-used-alisma-orientale-juzepzuk-in-chronic-kidney-disease
#17
Fang Dou, Hua Miao, Jing-Wen Wang, Lin Chen, Ming Wang, Hua Chen, Ai-Dong Wen, Ying-Yong Zhao
Alisma orientale Juzepzuk (AO) is widely used for various diuretic and nephropathic treatments in traditional Chinese medicines (TCM). In a clinical setting, AO is used as both a lipid-lowering and tubular interstitial fibrosis agent. However, the mechanisms of AO for the treatment of renal interstitial fibrosis and abnormal lipid metabolism are not well-understood. In this study, pharmacological and UPLC-HDMS-based lipidomic approaches were employed to investigate the lipid-lowering and tubular interstitial fibrosis effect of AO on rats with adenine-induced chronic kidney disease (CKD)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29472781/evaluation-of-traditional-medicinal-plant-cissus-setosa-roxb-vitaceae-for-antiulcer-property
#18
Chinnamaruthu Jayachitra, Senguttuvan Jamuna, Mohammad Ajmal Ali, Subramaniam Paulsamy, Fahad M A Al-Hemaid
Cissus setosa is an indigenous medicinal herb commonly used for the treatment of gastro ulcers. In the current investigation the aerial methanolic extract of C. setosa was investigated for their antiulcer activity using pylorus ligation and ethanol in experimental rats. The extract was administered at the doses of 200 and 400 mg/kg b.w. orally for 3 days. However, higher dose of the extract subsequently reduced gastric ulcer induced aberrations by pylorus ligation (70.05%) and ethanol (78.16%) as judged by their altered biochemical parameters such as free acidity, total acidity, total carbohydrate, total protein and pepsin activity...
February 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29472767/anti-hypertensive-and-cardioprotective-effects-of-a-novel-apitherapy-formulation-via-upregulation-of-peroxisome-proliferator-activated-receptor-%C3%AE-and-%C3%AE-in-spontaneous-hypertensive-rats
#19
Yanru Sun, Mingfeng Han, Zhenhuang Shen, Haibo Huang, Xiaoqing Miao
Ventricular remodeling is associated with many heart diseases, and ventricular remodeling induced by hypertension can be fatal independent of hypertension. In this study, we prepared a novel apitherapy formulation, designated Bao-Yuan-Ling (BYL), which contained propolis, royal jelly, and bee venom, to treat spontaneous hypertensive rats (SHRs). We then evaluated the pharmacology of BYL and the potential mechanisms through which BYL affects hypertension and ventricular remodeling. We found that BYL treatment could reduce blood pressure in SHRs...
February 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29472564/inhibitory-modulation-of-cytochrome-c-oxidase-activity-with-specific-near-infrared-light-wavelengths-attenuates-brain-ischemia-reperfusion-injury
#20
Thomas H Sanderson, Joseph M Wider, Icksoo Lee, Christian A Reynolds, Jenney Liu, Bradley Lepore, Reneé Tousignant, Melissa J Bukowski, Hollie Johnston, Alemu Fite, Sarita Raghunayakula, John Kamholz, Lawrence I Grossman, Karin Przyklenk, Maik Hüttemann
The interaction of light with biological tissue has been successfully utilized for multiple therapeutic purposes. Previous studies have suggested that near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase (COX) activity, which we confirmed for 810 nm NIR. In contrast, scanning the NIR spectrum between 700 nm and 1000 nm revealed two NIR wavelengths (750 nm and 950 nm) that reduced the activity of isolated COX. COX-inhibitory wavelengths reduced mitochondrial respiration, reduced the mitochondrial membrane potential (ΔΨm ), attenuated mitochondrial superoxide production, and attenuated neuronal death following oxygen glucose deprivation, whereas NIR that activates COX provided no benefit...
February 22, 2018: Scientific Reports
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