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https://www.readbyqxmd.com/read/27917125/comparison-of-liver-cell-models-using-the-basel-phenotyping-cocktail
#1
Benjamin Berger, Massimiliano Donzelli, Swarna Maseneni, Franziska Boess, Adrian Roth, Stephan Krähenbühl, Manuel Haschke
Currently used hepatocyte cell systems for in vitro assessment of drug metabolism include hepatoma cell lines and primary human hepatocyte (PHH) cultures. We investigated the suitability of the validated in vivo Basel phenotyping cocktail (caffeine [CYP1A2], efavirenz [CYP2B6], losartan [CYP2C9], omeprazole [CYP2C19], metoprolol [CYP2D6], midazolam [CYP3A4]) in vitro and characterized four hepatocyte cell systems (HepG2 cells, HepaRG cells, and primary cryopreserved human hepatocytes in 2-dimensional [2D] culture or in 3D-spheroid co-culture) regarding basal metabolism and CYP inducibility...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27903560/commonly-prescribed-drugs-associate-with-cognitive-function-a-cross-sectional-study-in-uk-biobank
#2
Alejo J Nevado-Holgado, Chi-Hun Kim, Laura Winchester, John Gallacher, Simon Lovestone
OBJECTIVE: To investigate medications associated with cognitive function. DESIGN: Population-based cross-sectional cohort study. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants aged 37-73 years who completed cognitive tests at the baseline visit in 2006-2010. MAIN OUTCOME MEASURES: Cognitive test outcomes on verbal-numerical reasoning test (n=165 493), memory test (n=482 766) and reaction time test (n=496 813)...
November 30, 2016: BMJ Open
https://www.readbyqxmd.com/read/27900443/p450bm3-fused-to-phosphite-dehydrogenase-allows-phosphite-driven-selective-oxidations
#3
Nina Beyer, Justyna K Kulig, Anette Bartsch, Martin A Hayes, Dick B Janssen, Marco W Fraaije
To facilitate the wider application of the NADPH-dependent P450BM3, we fused the monooxygenase with a phosphite dehydrogenase (PTDH). The resulting monooxygenase-dehydrogenase fusion enzyme acts as a self-sufficient bifunctional catalyst, accepting phosphite as a cheap electron donor for the regeneration of NADPH.The well-expressed fusion enzyme was purified and analyzed in comparison to the parent enzymes. Using lauric acid as substrate for P450BM3, it was found that the fusion enzyme had similar substrate affinity and hydroxylation selectivity while it displayed a significantly higher activity than the non-fused monooxygenase...
November 29, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27895392/determination-of-the-adequate-dosage-of-rebamipide-a-gastric-mucoprotective-drug-to-prevent-low-dose-aspirin-induced-gastrointestinal-mucosal-injury
#4
Kazuhiro Ota, Toshihisa Takeuchi, Sadaharu Nouda, Haruhiko Ozaki, Shinpei Kawaguchi, Yoshiaki Takahashi, Satoshi Harada, Shoko Edogawa, Yuichi Kojima, Takanori Kuramoto, Kazuhide Higuchi
Small intestinal mucosal injury caused by low-dose aspirin is a common cause of obscure gastrointestinal bleeding. We aimed to investigate the protective effects and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged 20-65 years) were included and divided into three groups. The groups received enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A: proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B: standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high-dose group)...
November 2016: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/27885694/pharmacokinetics-and-tolerability-of-a-new-formulation-of-omeprazole-in-the-horse
#5
A Di Salvo, S Busechian, F Zappulla, M C Marchesi, C Pieramati, S Orvieto, M Boveri, P G Predieri, F Rueca, G Della Rocca
A new formulation of omeprazole in gastro-resistant granules was tested with regard to its pharmacokinetics and tolerability. Twenty-four horses were randomly divided into three groups (8 horses/group) and treated, according a parallel study design, as follows: Group A untreated (control group), Group B received 4 mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which were treated orally once a day for 90 days. Blood samples, taken from Group B subjects during the 1st and the 29th day of treatment at pre-established time points, were used to determine the concentration-time curves of omeprazole...
November 24, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27883262/phytochemicals-enhance-antioxidant-enzyme-expression-to-protect-against-nsaid-induced-oxidative-damage-of-the-gastrointestinal-mucosa
#6
REVIEW
Yu-Ting Cheng, Chi-Cheng Lu, Gow-Chin Yen
The gastrointestinal mucosa provides the first protective barrier for digested food and xenobiotics, which are easily attacked by toxic substances. Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, diclofenac, indomethacin, and ketoprofen, are widely used in clinical medicine, but these drugs may cause oxidative stress, leading to gastrointestinal damage, such as ulcers. Lansoprazol, omeprazole, and other clinical drugs are widely used to treat duodenal and gastric ulcers and haven been shown to have multiple biological functions, such as antioxidant activity and the ability to upregulate antioxidant enzymes in vivo...
November 24, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27882460/development-of-a-specific-substrate-inhibitor-panel-liver-on-a-chip-for-evaluation-of-cytochrome-p450-activity
#7
A A Zakhariants, O A Burmistrova, M Y Shkurnikov, A A Poloznikov, D A Sakharov
We developed a cytochrome P450 substrate-inhibitor panel for preclinical in vitro evaluation of drugs in a 3D histotypical microfluidic cell model of human liver (liver-on-a-chip technology). The concentrations of substrates and inhibitors were optimized to ensure reliable detection of the principal metabolites by HPLC-mass-spectroscopy. The selected specific substrate-inhibitor pairs, namely bupropion/2-phenyl-2-(1-piperidinyl)propane) for evaluation of CYP2B6B activity, tolbutamide/sulfaphenazole for CYP2C9, omeprazole/(+)-N-benzylnirvanol for CYP2C19, and testosterone/ketoconazole for CYP3A4, enable reliable evaluation of the drug metabolism pathway...
November 23, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27882276/isolated-non-traumatic-bilateral-coronoid-process-fracture-of-the-mandible
#8
Nabil Al-Khalisi, Krishna Kumar, Natasha Acosta
Isolated bilateral fractures of the coronoid processes of the mandible occurred in this patient without any significant trauma. The definite etiology of this case is unknown, but possible causes or contributing factors may include acute reflex contraction of the patient's temporalis muscles leading to bilateral stress fractures, coronoid process hyperplasia, or the patient's long-term use of omeprazole. The planned treatment for this patient included pain control with Mobic and tramadol and splint fabrication followed by arch bar placement with training elastics for six weeks...
October 13, 2016: Curēus
https://www.readbyqxmd.com/read/27866273/omeprazole-suppressed-plasma-magnesium-level-and-duodenal-magnesium-absorption-in-male-sprague-dawley-rats
#9
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 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27865855/intestinal-response-to-salinity-challenge-in-the-senegalese-sole-solea-senegalensis
#10
I Ruiz-Jarabo, A Barany, I Jerez-Cepa, J M Mancera, J Fuentes
Fish are continuously forced to actively absorb or expel water and ions through epithelia. Most studies have focused on the gill due to its role in Na(+) and Cl(-) trafficking. However, comparatively few studies have focused on the changing function of the intestine in response to external salinity. Therefore, the present study investigated the main intestinal changes of long-term acclimation of the Senegalese sole (Solea senegalensis) to 5, 15, 38 and 55ppt. Through the measurement of short-circuit current (Isc) in Ussing chambers and biochemical approaches, we described a clear anterior/posterior functional regionalization of the intestine in response to salinity...
November 17, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27855237/insulin-autoimmune-syndrome-a-rare-cause-of-postprandial-hypoglycemia
#11
Pooja Sahni, Nitin Trivedi, Abdulkadir Omer
: A 65-year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels. She did not have any evidence for the use of oral antidiabetic medications, insulin, herbal substances, performing strenuous exercise or history of bariatric surgery. Fingerstick blood glucose readings revealed blood sugar of 35 mg/dL and 48 mg/dL, when she had these symptoms. Her medical history was significant for morbid obesity, hypothyroidism and gastro esophageal reflux disease...
2016: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/27842484/strong-induction-of-cytochrome-p450-1a-3a-but-not-p450-2b-in-cultured-hepatocytes-from-common-marmosets-and-cynomolgus-monkeys-by-typical-human-p450-inducing-agents
#12
Shotaro Uehara, Yasuhiro Uno, Takako Suzuki, Takashi Inoue, Masahiro Utoh, Erika Sasaki, Hiroshi Yamazaki
BACKGROUND: Common marmosets (Callithrix jacchus) and cynomolgus monkeys (Macaca fascicularis) are used as non-human primate models in preclinical studies for drug development. OBJECTIVE: The assessment of P450 induction in hepatocytes from marmosets and cynomolgus monkeys was performed using typical P450 inducers. METHODS: Induction of cytochrome P450 1-4 family enzymes was analyzed in two lots of cultured hepatocytes from common marmosets and cynomolgus monkeys after 24-h treatment with typical human P450 inducing agents by real-time reverse transcription-polymerase chain reaction...
November 14, 2016: Drug Metabolism Letters
https://www.readbyqxmd.com/read/27825331/preclinical-evaluation-of-anti-helicobacter-spp-activity-of-hippocratea-celastroides-kunth-and-its-acute-and-sub-acute-toxicity
#13
Griselda García-Alonso, Antonio Monroy-Noyola, Armando Contreras-Arellano, José Fernando Mariscal-Durand, Yolanda Gálvez-Molina, Alejandro Vázquez-Velázquez, Sara García-Jimenez, Pablo Nuñez, Alexandre Cardoso-Taketa, María Luisa Villarreal
BACKGROUND: Hippocratea celastroides Kunth, commonly known as "cancerina", is used in Mexican Traditional Medicine for the treatment of gastric and intestinal infections, systemic and skin inflammation, injuries and gastritis. The aim of this research was to assess the anti-Helicobacter pylori activities of hydro-ethanolic root-bark extracts from Hippocratea celastroides Kunth in naturally infected dogs, after testing their acute and subacute toxicities in mice. METHODS: To determine in vivo acute toxicity, a hydro-ethanolic extract was obtained and administered orally in female and male Balb-C mice, at doses ranging from 2000 to 5000 mg/kg...
November 8, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27820137/favorable-response-to-sirolimus-in-a-child-with-blue-rubber-bleb-nevus-syndrome-in-the-gastrointestinal-tract
#14
Aysel Ünlüsoy Aksu, Sinan Sari, Ödül Eğritaş Gürkan, Buket Dalgiç
Recently, sirolimus was demonstrated to be effective in treating vascular lesions and lessening the frequency of bleeding and secondary iron deficiency anemia. We present a child with blue rubber bleb nevus syndrome who had prolonged history of iron deficiency anemia secondary to unrecognized gastrointestinal bleeding. Treatment with propranolol, omeprazole and iron had failed. After 2.5 months of sirolimus therapy (trough levels 1 to 5 ng/mL), his hemoglobin concentration improved into the normal range and remained stable...
November 4, 2016: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/27818046/novel-mwcnts-graphene-oxide-pyrogallol-composite-with-enhanced-sensitivity-for-biosensing-applications
#15
Mona A Mohamed, Ali M Yehia, Craig E Banks, Nageh K Allam
A novel and highly sensitive biosensor employing graphene oxide nano-sheets (GO), multiwalled carbon nanotubes (MWCNTs), and pyrogallol (PG) was fabricated and utilized for the sensitive determination of omeprazole (OME). The morphological and structural features of the composite material were characterized using different techniques. The modified electrode showed a remarkable improvement in the anodic oxidation activity of OME due to the enhancement in the current response compared to the bare carbon paste electrode (CPE)...
October 11, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27810953/weight-gain-in-mice-on-a-high-caloric-diet-and-chronically-treated-with-omeprazole-depends-on-sex-and-genetic-background
#16
Milena Saqui-Salces, Amy C Tsao, Merritt G Gillilland, Juanita L Merchant
: The impact of omeprazole (OM), a widely used over-the-counter proton pump inhibitor, on weight gain has not been extensively explored. We examined what factors, e.g., diet composition, microbiota, genetic strain and sex, might affect weight gain in mice fed a high caloric diet while on OM. METHODS: Inbred C57BL/6J strain, a 50:50 hybrid (B6SJLF1/J) strain and mice on a highly mixed genetic background were fed four diets: standard chow (STD, 6% fat), STD with 200 ppm OM (STD+O), a high-energy chow (HiE, 11% fat) and HiE chow with OM (HiE+O) for 17 weeks...
November 3, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27810562/improved-oral-absorption-profile-of-itraconazole-in-hypochlorhydria-by-self-micellizing-solid-dispersion-approach
#17
Yoshiki Kojo, Saori Matsunaga, Hiroki Suzuki, Hideyuki Sato, Yoshiki Seto, Satomi Onoue
The present study was aimed to evaluate the applicability of a self-micellizing solid dispersion (SMSD) system of itraconazole (ITZ) with the use of Soluplus(®) to achieve improved dissolution and stable oral absorption of ITZ under hypochlorhydric conditions. The SMSD of ITZ (SMSD/ITZ) was prepared by the freeze-drying method. Physicochemical properties of SMSD/ITZ were assessed in terms of morphology, crystallinity, particle size, thermal behavior, dissolution profile, and stability. The pharmacokinetic profile of SMSD/ITZ was evaluated in both normal rats and omeprazole-treated rats as a hypochlorhydric model...
October 31, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27808485/concomitant-use-of-proton-pump-inhibitors-and-dual-antiplatelet-therapy-for-cardiovascular-outcomes
#18
Alessandro Mandurino-Mirizzi, Sergio Leonardi, Chiara Melloni
INTRODUCTION: The aim of this review is to discuss the consequences of potential pharmacokinetic interactions between proton pump inhibitors (PPIs) and antiplatelet therapy on cardiovascular (CV) outcomes and provide guidance on the management of concomitant use of PPIs in patients on dual antiplatelet therapy (DAPT). EVIDENCE ACQUISITION: DAPT combining aspirin and oral P2Y12 receptor inhibitors increases the risk of gastrointestinal (GI) bleeding, with higher rates of morbidity and mortality in patients undergoing percutaneous coronary intervention (PCI)...
November 3, 2016: Minerva Endocrinologica
https://www.readbyqxmd.com/read/27806489/the-effect-of-oral-administration-of-pistacia-atlantica-kurdica-gum-on-the-eradication-of-helicobacter-pylori-in-patients-with-dyspepsia-a-randomized-clinical-trial
#19
Hamidollah Afrasiabian, Mohammad Hadi Imanieh, Mohammad Ali Nejati, Alireza Salehi
H. pylori infection is one of the most common infections in the world so that the aim of this study was to evaluate the antimicrobial P. Atlantica Kurdica gum in the eradication of H. pylori. This study is a randomized clinical trial; Patients with positive Urea Breath Test and symptoms of dyspepsia were entered. Patients were randomly divided into four groups. Group A: three drugs including 500 mg of Amoxicillin twice a day (bd), Clarithromycin 500 mg bd and Omeprazole 20 mg (bd) and Group B: Group A drugs plus the capsule containing 1 g of powdered P...
July 21, 2016: Global Journal of Health Science
https://www.readbyqxmd.com/read/27801778/antiviral-screening-of-multiple-compounds-against-ebola-virus
#20
Stuart D Dowall, Kevin Bewley, Robert J Watson, Seshadri S Vasan, Chandradhish Ghosh, Mohini M Konai, Gro Gausdal, James B Lorens, Jason Long, Wendy Barclay, Isabel Garcia-Dorival, Julian Hiscox, Andrew Bosworth, Irene Taylor, Linda Easterbrook, James Pitman, Sian Summers, Jenny Chan-Pensley, Simon Funnell, Julia Vipond, Sue Charlton, Jayanta Haldar, Roger Hewson, Miles W Carroll
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests...
October 27, 2016: Viruses
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