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Protein pump inhibitor

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https://www.readbyqxmd.com/read/27895902/effect-of-%C3%AE-lactamase-inhibitors-on-in-vitro-activity-of-%C3%AE-lactam-antibiotics-against-burkholderia-cepacia-complex-species
#1
Annelien Everaert, Tom Coenye
BACKGROUND: Bacteria belonging to the Burkholderia cepacia complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients. Intrinsic resistance to a wide range of antimicrobial agents, including a variety of β-lactam antibiotics, is frequently observed in Bcc strains. Resistance to β-lactams is most commonly mediated by efflux pumps, alterations in penicillin-binding proteins or the expression of β-lactamases. β-lactamase inhibitors are able to restore the in vitro activity of β-lactam molecules against a variety of Gram-negative species, but the effect of these inhibitors on the activity of β-lactam treatment against Bcc species is still poorly investigated...
2016: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/27866273/omeprazole-suppressed-plasma-magnesium-level-and-duodenal-magnesium-absorption-in-male-sprague-dawley-rats
#2
Narongrit Thongon, Jirawat Penguy, Sasikan Kulwong, Kanyanat Khongmueang, Matthana Thongma
Hypomagnesemia is the most concerned side effect of proton pump inhibitors (PPIs) in chronic users. However, the mechanism of PPIs-induced systemic Mg(2+) deficit is currently unclear. The present study aimed to elucidate the direct effect of short-term and long-term PPIs administrations on whole body Mg(2+) homeostasis and duodenal Mg(2+) absorption in rats. Mg(2+) homeostasis was studied by determining the serum Mg(2+) level, urine and fecal Mg(2+) excretions, and bone and muscle Mg(2+) contents. Duodenal Mg(2+) absorption as well as paracellular charge selectivity were studied...
November 19, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27855620/mrp1-dependent-collateral-sensitivity-of-multidrug-resistant-cancer-cells-identifying-selective-modulators-inducing-cellular-glutathione-depletion
#3
Doriane Lorendeau, Lauriane Dury, Rachad Nasr, Ahcène Boumendjel, Elisabetta Teodori, Michael Gütschow, Pierre Falson, Attilio Di Pietro, Hélène Baubichon-Cortay
Cancer cells are permanently being selected for survival and proliferation. During this process, tumor cells often co-opt basic physiological mechanisms to protect themselves from toxic chemotherapy. One of these mechanisms is the overexpression of ATP-binding cassette (ABC) drug efflux pumps leading to multidrug resistance (MDR) of cancer cells through an increase of drug efflux. In the past 20 years, many efforts were done to circumvent MDR through the inhibition of ABC transporters. A number of inhibitors of these transporters were found but are rarely specific or rationally developed...
November 18, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27822201/a-tolc-like-protein-of-actinobacillus-pleuropneumoniae-is-involved-in-antibiotic-resistance-and-biofilm-formation
#4
Ying Li, Sanjie Cao, Luhua Zhang, Gee W Lau, Yiping Wen, Rui Wu, Qin Zhao, Xiaobo Huang, Qigui Yan, Yong Huang, Xintian Wen
Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a significant disease that causes serious economic losses to the swine industry worldwide. Persistent infections caused by bacterial biofilms are recalcitrant to treat because of the particular drug resistance of biofilm-dwelling cells. TolC, a key component of multidrug efflux pumps, are responsible for multidrug resistance (MDR) in many Gram-negative bacteria. In this study, we identified two TolC-like proteins, TolC1 and TolC2, in A...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27815466/fluorinated-beta-diketo-phosphorus-ylides-are-novel-efflux-pump-inhibitors-in-bacteria
#5
Annamária Kincses, Ágnes Míra Szabó, Ryosuke Saijo, Genki Watanabe, Masami Kawase, Joseph Molnár, Gabriella Spengler
BACKGROUND: One of the most important resistance mechanisms in bacteria is the increased expression of multidrug efflux pumps. To combat efflux-related resistance, the development of new efflux pump inhibitors is essential. MATERIALS AND METHODS: Ten phosphorus ylides were compared based on their MDR-reverting activity in multidrug efflux pump system consisting of the subunits acridine-resistance proteins A and B (AcrA and AcrB) and the multidrug efflux pump outer membrane factor TolC (TolC) of Escherichia coli K-12 AG100 strain and its AcrAB-TolC-deleted strain...
November 2016: In Vivo
https://www.readbyqxmd.com/read/27814643/cellular-efflux-transporters-and-the-potential-role-of-natural-products-in-combating-efflux-mediated-drug-resistance
#6
Muhammad Ayaz, Fazal Subhan, Abdul Sadiq, Farhat Ullah, Jawad Ahmed, Robert D E Sewell
Efflux mediated multidrug resistance (MDR) is a major problem in the treatment of bacterial, fungal and protozoal infections in addition to cancer chemotherapy. Among other well known mechanisms, efflux pumps are significant contributors to chemo-resistance. Efflux mediated resistance generally occurs through up-regulation of genes responsible for the expression of transporter proteins extruding drugs from the cell to create intracellular sub-therapeutic concentrations leading to resistance. The rapid expansion of MDR pathogens necessitates the discovery of resistance modifying drugs, which in combination with antimicrobial or chemotherapeutic agents would tend to reinstate the action of these drugs and avert the emergence of acquired resistance...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27810576/effects-of-pharmaceuticals-and-personal-care-products-ppcps-on-multixenobiotic-resistance-mxr-related-efflux-transporter-activity-in-zebrafish-danio-rerio-embryos
#7
V Cunha, K Burkhardt-Medicke, P Wellner, M M Santos, P Moradas-Ferreira, T Luckenbach, M Ferreira
Certain ATP binding cassette (ABC) transporter proteins, such as zebrafish Abcb4, are efflux pumps acting as a cellular defence against a wide range of different, potentially toxic chemical compounds thus mediating so called multixenobiotic resistance (MXR). Certain chemicals target MXR proteins and, as so called chemosensitisers, inhibit the activity of these proteins thus increasing the toxicity of other chemicals that would normally be effluxed. In this study 14 pharmaceuticals and personal care products (PPCPs) that are being increasingly detected in aquatic systems, were assessed for interference with the MXR system of zebrafish (Danio rerio)...
October 28, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27771990/spectroscopic-and-molecular-modeling-approaches-to-investigate-the-binding-of-proton-pump-inhibitors-to-human-serum-albumin
#8
Suma K Pawar, Reeta Punith, Roopa S Naik, J Seetharamappa
The interaction between two proton pump inhibitors viz., omeprazole (OME) and esomeprazole (EPZ) with human serum albumin (HSA) was studied by fluorescence, absorption, circular dichroism (CD), fourier transform infrared spectroscopy (FT-IR), voltammetry and molecular modeling approaches. The Stern-Volmer quenching constants (Ksv) for OME-HSA and EPZ-HSA systems obtained at different temperatures revealed that both OME and EPZ quenched the intensity of HSA through dynamic mode of quenching mechanism. The binding constants of OME-HSA and EPZ-HSA increased with temperature, indicating the increased stability of these systems at higher temperatures...
October 24, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27769859/chop-deficiency-inhibits-methylglyoxal-induced-endothelial-dysfunction
#9
Yoon Young Choi, Suji Kim, Jung-Hwa Han, Dae-Hwan Nam, Kwon Moo Park, Seong Yong Kim, Chang-Hoon Woo
Epidemiological studies suggested that diabetic patients are susceptible to develop cardiovascular complications along with having endothelial dysfunction. It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction rather than glucose itself. Here, we investigated the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress. Biochemical data showed that 4-PBA significantly inhibited MGO-induced protein cleavages of PARP-1 and caspase-3...
October 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27768847/reviving-antibiotics-efflux-pump-inhibitors-that-interact-with-acra-a-membrane-fusion-protein-of-the-acrab-tolc-multidrug-efflux-pump
#10
Narges Abdali, Jerry M Parks, Keith M Haynes, Julie L Chaney, Adam T Green, David Wolloscheck, John K Walker, Valentin V Rybenkov, Jerome Baudry, Jeremy C Smith, Helen I Zgurskaya
Antibiotic resistance is a major threat to human welfare. Inhibitors of multidrug efflux pumps (EPIs) are promising alternative therapeutics that could revive activities of antibiotics and reduce bacterial virulence. Identification of new druggable sites for inhibition is critical for the development of effective EPIs, especially in light of constantly emerging resistance. Here, we describe EPIs that interact with periplasmic membrane fusion proteins, critical components of efflux pumps that are responsible for the activation of the transporter and the recruitment of the outer-membrane channel...
November 2, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27758861/hydrogen-bonding-to-the-substrate-is-not-required-for-rieske-iron-sulfur-protein-docking-to-the-quinol-oxidation-site-of-complex-iii
#11
Lothar Esser, Fei Zhou, Yihui Zhou, Yumei Xiao, Wai-Kwan Tang, Chang-An Yu, Zhaohai Qin, Di Xia
Complex III or the cytochrome (cyt) bc1 complex constitutes an integral part of the respiratory chain of most aerobic organisms and of the photosynthetic apparatus of anoxygenic purple bacteria. The function of cyt bc1 is to couple the reaction of electron transfer from ubiquinol to cytochrome c to proton pumping across the membrane. Mechanistically, the electron transfer reaction requires docking of its Rieske iron-sulfur protein (ISP) subunit to the quinol oxidation site (QP) of the complex. Formation of an H-bond between the ISP and the bound substrate was proposed to mediate the docking...
November 25, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27754177/sy-15-4-role-of-histone-deacetylases-in-regulating-endothelial-and-vascular-function
#12
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753987/sy-10-1-renal-glucose-handling-and-sglt2
#13
Resham Poudel
The kidneys maintain glucose homeostasis through its utilization, gluconeogenesis, and reabsorption. Glucose is freely filtered and reabsorbed in order to retain energy essential between meals. The amount of glucose reabsorbed by the kidneys is equivalent to the amount entering the filtration system. With a daily glomerular filtration rate of 180 L, approximately 180 g (180 L/day × 100 mg/dL) of glucose must be reabsorbed each day to maintain an average fasting plasma glucose concentration of 5.6 mmol/L (100 mg/dL)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753464/using-chemical-probes-to-assess-the-feasibility-of-targeting-seca-for-developing-antimicrobial-agents-against-gram-negative-bacteria
#14
Jinshan Jin, Ying-Hsin Hsieh, Jianmei Cui, Krishna Damera, Chaofeng Dai, Arpana S Chaudhary, Hao Zhang, Hsiuchin Yang, Nannan Cao, Chun Jiang, Martti Vaara, Binghe Wang, Phang C Tai
With the widespread emergence of drug resistance, there is an urgent need to search for new antimicrobials, especially those against Gram-negative bacteria. Along this line, the identification of viable targets is a critical first step. The protein translocase SecA is commonly believed to be an excellent target for the development of broad-spectrum antimicrobials. In recent years, we developed three structural classes of SecA inhibitors that have proven to be very effective against Gram-positive bacteria. However, we have not achieved the same level of success against Gram-negative bacteria, despite the potent inhibition of SecA in enzyme assays by the same inhibitors...
November 21, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27752976/pharmacogenomics-and-pharmacogenetics-for-the-intensive-care-unit-a-narrative-review
#15
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/27737557/structure-function-profile-of-mmpl3-the-essential-mycolic-acid-transporter-from-mycobacterium-tuberculosis
#16
Juan Manuel Belardinelli, Amira Yazidi, Liang Yang, Lucien Fabre, Wei Li, Benoit Jacques, Shiva Kumar Angala, Isabelle Rouiller, Helen I Zgurskaya, Jurgen Sygusch, Mary Jackson
The MmpL family of proteins translocates complex (glyco)lipids and siderophores across the cell envelope of mycobacteria and closely related Corynebacteriaceae and plays important roles in the biogenesis of the outer membrane of these organisms. Despite their significance in the physiology and virulence of Mycobacterium tuberculosis, and from the perspective of developing novel antituberculosis agents, little is known about their structure and mechanism of translocation. In this study, the essential mycobacterial mycolic acid transporter, MmpL3, and its orthologue in Corynebacterium glutamicum, CmpL1, were investigated as prototypical MmpL proteins to gain insight into the transmembrane topology, tertiary and quaternary structures, and functional regions of this transporter family...
October 14, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27735867/modulation-of-autophagy-by-a-thioxanthone-decreases-the-viability-of-melanoma-cells
#17
Raquel T Lima, Diana Sousa, Ana M Paiva, Andreia Palmeira, João Barbosa, Madalena Pedro, Madalena M Pinto, Emília Sousa, M Helena Vasconcelos
(1) Background: Our previous studies unveiled the hit thioxanthone TXA1 as an inhibitor of P-glycoprotein (drug efflux pump) and of human tumor cells growth, namely of melanoma cells. Since TXA1 is structurally similar to lucanthone (an autophagy inhibitor and apoptosis inducer) and to N(10)-substituted phenoxazines (isosteres of thioxanthones, and autophagy inducers), this study aimed at further assessing its cytotoxic mechanism and evaluating its potential as an autophagy modulator in A375-C5 melanoma cells; (2) Methods: Flow cytometry with propidium iodide (PI) for cell cycle profile analysis; Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, flow cytometry with Annexin V/PI labeling and Western blot for apoptosis analysis were conducted...
October 10, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27734291/clinical-pharmacokinetics-and-pharmacodynamics-of-cabozantinib
#18
Steven A Lacy, Dale R Miles, Linh T Nguyen
Cabozantinib inhibits receptor tyrosine kinases involved in tumor angiogenesis and metastasis. The capsule formulation (Cometriq(®)) is approved for the treatment of progressive metastatic medullary thyroid cancer at a 140-mg free base equivalent dose. The tablet formulation (Cabometyx™, 60-mg free base equivalent dose) is approved for the treatment of renal cell carcinoma following anti-angiogenic therapy. Cabozantinib displays a long terminal plasma half-life (~120 h) and accumulates ~fivefold by day 15 following daily dosing based on area under the plasma concentration-time curve (AUC)...
October 12, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27725188/omeprazole-induces-heme-oxygenase-1-in-fetal-human-pulmonary-microvascular-endothelial-cells-via-hydrogen-peroxide-independent-nrf2-signaling-pathway
#19
Ananddeep Patel, Shaojie Zhang, Amrit Kumar Shrestha, Paramahamsa Maturu, Bhagavatula Moorthy, Binoy Shivanna
Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC...
November 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27717558/proton-pump-inhibitors-decrease-eotaxin-3-ccl26-expression-in-patients-with-chronic-rhinosinusitis-with-nasal-polyps-possible-role-of-the-nongastric-h-k-atpase
#20
Jin-Young Min, Christopher J Ocampo, Whitney W Stevens, Caroline P E Price, Christopher F Thompson, Tetsuya Homma, Julia H Huang, James E Norton, Lydia A Suh, Kathryn L Pothoven, David B Conley, Kevin C Welch, Stephanie Shintani-Smith, Anju T Peters, Leslie C Grammer, Kathleen E Harris, Kathryn E Hulse, Atsushi Kato, Nikolai N Modyanov, Robert C Kern, Robert P Schleimer, Bruce K Tan
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by tissue eosinophilia that is associated with poor prognosis. Recent findings that proton pump inhibitors (PPIs) directly modulate the expression of eotaxin-3, an eosinophil chemoattractant, in patients with eosinophilic diseases suggest therapeutic potential for PPIs in those with CRSwNP. OBJECTIVE: We assessed the effect of type 2 mediators, particularly IL-13 and eotaxin-3, on tissue eosinophilia and disease severity in patients with chronic rhinosinusitis (CRS)...
October 4, 2016: Journal of Allergy and Clinical Immunology
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