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Protein pump inhibitor

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https://www.readbyqxmd.com/read/28212798/protein-kinase-c-as-regulator-of-vascular-smooth-muscle-function-and-potential-target-in-vascular-disorders
#1
H C Ringvold, R A Khalil
Vascular smooth muscle (VSM) plays an important role in maintaining vascular tone. In addition to Ca(2+)-dependent myosin light chain (MLC) phosphorylation, protein kinase C (PKC) is a major regulator of VSM function. PKC is a family of conventional Ca(2+)-dependent α, β, and γ, novel Ca(2+)-independent δ, ɛ, θ, and η, and atypical ξ, and ι/λ isoforms. Inactive PKC is mainly cytosolic, and upon activation it undergoes phosphorylation, maturation, and translocation to the surface membrane, the nucleus, endoplasmic reticulum, and other cell organelles; a process facilitated by scaffold proteins such as RACKs...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28202577/nimesulide-and-4-hydroxynimesulide-as-bile-acid-transporters-inhibitors-are-contributory-factors-for-drug-induced-cholestasis
#2
Lei Zhou, Xiaoyan Pang, Jingfang Jiang, Dafang Zhong, Xiaoyan Chen
Nimesulide (NIM) is a classic nonsteroidal anti-inflammatory drug. However, some patients treated with NIM suffered from cholestatic liver injury. For this reason, we investigated the potential mechanism underlying NIM-induced cholestasis by using in vivo and in vitro models. Oral administration of 100 mg/kg/day NIM to Wistar rats for 5 days increased the levels of plasma total bile acids, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase by 1.49-, 1.31-, 1.60-, and 1.29-fold, respectively...
February 15, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28186681/skin-derived-precursors-as-a-source-of-progenitors-for-corneal-endothelial-regeneration
#3
Emi Inagaki, Shin Hatou, Kazunari Higa, Satoru Yoshida, Shinsuke Shibata, Hideyuki Okano, Kazuo Tsubota, Shigeto Shimmura
Corneal blindness is the fourth leading cause of blindness in the world. Current treatment is allogenic corneal transplantation, which is limited by shortage of donors and immunological rejection. Skin-derived precursors (SKPs) are postnatal stem cells, which are self-renewing, multipotent precursors that can be isolated and expanded from the dermis. Facial skin may therefore be an accessible autologous source of neural crest derived cells. SKPs were isolated from facial skin of Wnt1-Cre/Floxed EGFP mouse. After inducing differentiation with medium containing retinoic acid and GSK 3-β inhibitor, SKPs formed polygonal corneal endothelial-like cells (sTECE)...
February 6, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28177671/the-effect-of-short-term-oral-treatment-with-omeprazole-or-pantoprazole-on-the-function-of-polymorphonuclear-neutrophils
#4
Maja Kostrzewska, Marzena Garley, Wioletta Ratajczak, Ewa Jablonska, Jacek Jamiołkowski, Andrzej Dabrowski
Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We have evaluated the effect of omeprazole and pantoprazole treatment on the PMNs function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results...
January 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28156030/er-to-golgi-blockade-of-nascent-desmosomal-cadherins-in-serca2-inhibited-keratinocytes-implications-for-darier-s-disease
#5
Ning Li, Moonhee Park, Shengxiang Xiao, Zhi Liu, Luis A Diaz
Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in SERCA2, a Ca(2+) pump that transports Ca(2+) from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca(2+) -dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by two distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER-to-Golgi transport of nascent DC is blocked...
February 3, 2017: Traffic
https://www.readbyqxmd.com/read/28139517/role-of-jagged1-hey1-signal-in-angiotensin-ii-induced-impairment-of-myocardial-angiogenesis
#6
Ai-Li Guan, Tao He, Yi-Bing Shao, Yi-Fan Chi, Hong-Yan Dai, Yan Wang, Li Xu, Xuan Yang, Hua-Min Ding, Shang-Lang Cai
BACKGROUND: Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28138903/the-treatment-of-giant-cell-arteritis
#7
REVIEW
Imran Jivraj, Madhura Tamhankar
Giant cell arteritis (GCA) is a systemic inflammatory vasculitis affecting medium and large vessels with potentially sight and life-threatening complications. Early diagnosis and prompt treatment are imperative in order to prevent vision loss and progression of the disease. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are inflammatory markers which are elevated in the majority of patients and support the diagnosis of GCA among patients who present with typical symptoms. GCA is confirmed with superficial temporal artery biopsy which demonstrates characteristic pathological findings...
January 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28128097/high-level-resistance-to-meropenem-in-clinical-isolates-of-pseudomonas-aeruginosa-in-the-absence-of-carbapenemases-role-of-active-efflux-and-porin-alterations
#8
Hussein Chalhoub, Yolanda Sáenz, Hector Rodriguez-Villalobos, Olivier Denis, Barbara C Kahl, Paul M Tulkens, Françoise Van Bambeke
High-level carbapenem resistance is worryingly increasing in clinical isolates and is often attributed to carbapenemase expression. This study aimed to determine the mechanisms leading to high-level meropenem resistance in six carbapenemase-negative Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients and seven carbapenemase-positive isolates from patients suffering from hospital-acquired pneumonia (HAP). MICs were determined in the absence or presence of l-arginine or glycine-glutamate as competitive substrates for OprD (OccD1) or OpdP (OccD3), respectively, or the efflux pump inhibitor Phe-Arg β-naphthylamide (PAβN)...
December 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28113597/on-chip-bioelectric-impedance-spectroscopy-reveals-the-effect-of-p-glycoprotein-efflux-pumps-on-the-paracellular-impedance-of-tight-junctions-at-the-blood-brain-barrier
#9
Ramsey Kraya, Alexander Komin, Peter Searson
Bioelectric impedance spectroscopy was used to elucidate the influence of P-gp efflux pumps on the kinetics of tight junction down-regulation in confluent monolayers of Madine Darby Canine Kidney Epithelial Cells (MDCK) following administration of phenylarsine oxide (PAO), a molecule that inhibits protein tyrosine phosphatases (PTP) and induces matrix metalloproteinase activity. Matrix metalloproteinases (MMPs) and phosphatase inhibitors induce modification of occludin tight junction proteins critical for the proper function of the blood-brain barrier...
August 30, 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28096160/determinants-of-antibacterial-spectrum-and-resistance-potential-of-the-elongation-factor-g-inhibitor-argyrin-b-in-key-gram-negative-pathogens
#10
Adriana K Jones, Angela L Woods, Kenneth T Takeoka, Xiaoyu Shen, Jun-Rong Wei, Ruth E Caughlan, Charles R Dean
Argyrins are natural products with antibacterial activity against Gram-negative pathogens such as P. aeruginosa, B. multivorans and S. maltophilia We previously showed that argyrin B targets elongation factor G (FusA). Here we show that Argyrin B activity against P. aeruginosa PAO1 (MIC = 8 μg/mL) was not affected by deletion of the MexAB-OprM, MexXY-OprM, MexCD-OprJ or MexEF-OprN efflux pumps. However, argyrin B induced expression of MexXY causing a slight but reproducible antagonism with the MexXY substrate antibiotic ciprofloxacin...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28052644/effect-of-thymol-on-ca%C3%A2-%C3%A2-%C2%BA-homeostasis-and-viability-in-pc3-human-prostate-cancer-cells
#11
Jeng-Hsien Yeh, Chiang-Ting Chou, I-Shu Chen, Ti Lu, Ko-Long Lin, Chia-Cheng Yu, Wei-Zhe Liang, Hong-Tai Chang, Chun-Chi Kuo, Chin-Man Ho, Wen-Teng Chang, Pochuen Shieh, Chung-Ren Jan
Thymol is a phenolic compound that affects physiology in different cell models. However, whether thymol affects Ca²⁺ homeostasis in prostate cancer cells is unknown. The action of this compound on cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and viability in PC3 human prostate cancer cells was explored. The results show that thymol at concentrations of 100-1500 μM caused [Ca²⁺]i rises in a concentration-dependent manner. Removal of extracellular Ca²⁺ reduced thymol’s effect by approximately 80%...
28, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/28039570/different-transcriptional-profiling-between-senescent-and-non-senescent-human-coronary-artery-endothelial-cells-hcaecs-by-omeprazole-and-lansoprazole-treatment
#12
Laura Costarelli, Robertina Giacconi, Marco Malavolta, Andrea Basso, Francesco Piacenza, Mauro Provinciali, Marcello G Maggio, Andrea Corsonello, Fabrizia Lattanzio
Recent evidence suggests that high dose and/or long term use of proton pump inhibitors (PPIs) may increase the risk of adverse cardiovascular events in older patients, but mechanisms underlying these detrimental effects are not known. Taking into account that the senescent endothelial cells have been implicated in the genesis or promotion of age-related cardiovascular disease, we hypothesized an active role of PPIs in senescent cells. The aim of this study is to investigate the changes in gene expression occurring in senescent and non-senescent human coronary artery endothelial cells (HCAECs) following Omeprazole (OPZ) or Lansoprazole (LPZ) treatment...
December 30, 2016: Biogerontology
https://www.readbyqxmd.com/read/28034583/differential-hypertensive-protease-expression-in-the-thoracic-versus-abdominal-aorta
#13
Jean Marie Ruddy, Adam W Akerman, Denise Kimbrough, Elizabeth K Nadeau, Robert E Stroud, Rupak Mukherjee, John S Ikonomidis, Jeffrey A Jones
BACKGROUND: Hypertension (HTN), which is a major risk factor for cardiovascular morbidity and mortality, can drive pathologic remodeling of the macro- and microcirculation. Patterns of aortic pathology differ, however, suggesting regional heterogeneity of the pressure-sensitive protease systems triggering extracellular matrix remodeling in the thoracic (TA) and abdominal aortas (AA). This study tested the hypothesis that the expression of two major protease systems (matrix metalloproteinases [MMPs] and cathepsins) in the TA and AA would be differentially affected with HTN...
December 26, 2016: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28032595/prospective-identification-of-resistance-mechanisms-to-hsp90-inhibition-in-kras-mutant-cancer-cells
#14
Arefeh Rouhi, Christina Miller, Sarah Grasedieck, Stefanie Reinhart, Britta Stolze, Hartmut Döhner, Florian Kuchenbauer, Lars Bullinger, Stefan Fröhling, Claudia Scholl
Inhibition of the HSP90 chaperone results in depletion of many signaling proteins that drive tumorigenesis, such as downstream effectors of KRAS, the most commonly mutated human oncogene. As a consequence, several small-molecule HSP90 inhibitors are being evaluated in clinical trials as anticancer agents. To prospectively identify mechanisms through which HSP90-dependent cancer cells evade pharmacologic HSP90 blockade, we generated multiple mutant KRAS-driven cancer cell lines with acquired resistance to the purine-scaffold HSP90 inhibitor PU-H71...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28029615/on-chip-bioelectric-impedance-spectroscopy-reveals-the-effect-of-p-glycoprotein-efflux-pumps-on-the-paracellular-impedance-of-tight-junctions-at-the-blood-brain-barrier
#15
Ramsey Kraya, Alexander Komin, Peter Searson
Bioelectric impedance spectroscopy was used to elucidate the influence of P-gp efflux pumps on the kinetics of tight junction down-regulation in confluent monolayers of Madine Darby Canine Kidney Epithelial Cells (MDCK) following administration of phenylarsine oxide (PAO), a molecule that inhibits protein tyrosine phosphatases (PTP) and induces matrix metalloproteinase activity. Matrix metalloproteinases (MMPs) and phosphatase inhibitors induce modification of occludin tight junction proteins critical for the proper function of the blood-brain barrier...
October 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/27996295/medicinal-plants-for-management-of-gastroesophageal-reflux-disease-a-review-of-animal-and-human-studies
#16
Mehdi Salehi, Hossein Karegar-Borzi, Mehrdad Karimi, Roja Rahimi
OBJECTIVES: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disease that causes troublesome symptoms and/or complications. The major therapeutic strategy for GERD focuses mainly on symptom alleviation using proton pump inhibitors (PPIs), which does not produce a perfect response in all patients. An approach with new therapeutic agents for GERD seems to be essential. The aim of this study was to review animal and human studies investigating the effect of medicinal plants in GERD as well as mechanisms underlying their therapeutic effects...
February 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/27991740/determination-of-rabeprazole-enantiomers-in-dog-plasma-by-supercritical-fluid-chromatography-tandem-mass-spectrometry-and-its-application-to-a-pharmacokinetic-study
#17
Chong Su, Hong Yang, Xiangjun Meng, J Paul Fawcett, Jianming Cao, Yan Yang, Jingkai Gu
Rabeprazole is a novel benzimidazole proton pump inhibitor used for the treatment of gastrointestinal disorders. It is a chiral molecule that gives rise to the possibility of stereoselective pharmacokinetics. To investigate this phenomenon, a rapid and sensitive chiral assay based on supercritical fluid chromatography tandem mass spectrometry was developed and applied to the determination of (R)-rabeprazole and (S)-rabeprazole in dog plasma. Sample preparation involved protein precipitation with acetonitrile after addition of (R)-lansoprazole as internal standard...
December 19, 2016: Journal of Separation Science
https://www.readbyqxmd.com/read/27960647/proton-pump-inhibitors-use-suppresses-iron-absorption-in-congenital-dyserythropoietic-anemia
#18
Hanna Shalev, Abed Abu Quider, Miriam Ben Harosh, Josef Kapelushnik
Congenital dyserythropoietic anemia type I (CDA I) is associated, as other anemic noninflammatory states, with ineffective erythropoiesis and increased iron absorption, which may lead to complication of iron overload. The latter complication requires iron-chelating therapy, which may be associated with adverse effects and toxicity. Gastric acid production is known to be an important factor that facilitates non-heme iron absorption. The purpose of this study was to examine whether treatment with proton pump inhibitors (PPIs) can decrease iron absorption in patients with CDA I...
October 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27940051/attenuated-jnk-signaling-in-multidrug-resistant-leukemic-cells-dual-role-of-mapk-in-cell-survival
#19
David Cerezo, Antonio J Ruiz-Alcaraz, Miriam Lencina-Guardiola, Manuel Cánovas, Pilar García-Peñarrubia, Inmaculada Martínez-López, Elena Martín-Orozco
Having found previously that leukemic cells with multidrug resistant (MDR) phenotype, but not their sensitive counterparts, exhibit collateral sensitivity to cold stress in a P-gp-dependent manner, our aim was to study the signaling pathways involved in this phenomenon in sensitive (L1210) and resistant cells (L1210R and CBMC-6). It was observed that the acquisition of MDR phenotype by leukemic cells or their transfection with the extrussion pump, P-gp, modifies the activation profile and regulation of Mitogen-Activated Protein Kinases (MAPK) in cells exposed to low temperatures...
January 2017: Cellular Signalling
https://www.readbyqxmd.com/read/27916771/a-case-of-left-subphrenic-abscess-caused-by-gastric-ulcer-penetration-that-was-successfully-treated-with-endoscopic-transgastric-drainage
#20
Yuki Hanaoka, Dai Sugimoto, Hiroshi Nakamura, Hiroko Yamashita, Hiroaki Igarashi, Itsuro Ogata
A 65-year-old male visited our hospital because of fever and difficulty in walking. He was suffering from left-sided hypochondrial pain for a month. Laboratory tests performed on admission revealed a white blood cell count of 1700/μl and C-reactive protein level of 9.51mg/dl, which were suggestive of severe inflammation. Contrast-enhanced computed tomography revealed a subphrenic abscess around the spleen, which we considered to be caused by gastric penetration into the gastrosplenic ligament. Upper esophagogastroduodenoscopy revealed a gastric ulcer together with a fistula that connected to the left subphrenic abscess...
2016: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
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