Read by QxMD icon Read

Pharmacology Research & Perspectives

Khaled A Shibany, Sabine Tötemeyer, Stefanie L Pratt, Stuart W Paine
Despite reports of the successful isolation of primary equine hepatocytes, there are no published data regarding the successful cryopreservation of these isolated cells. In this study, a detailed description of the procedures for isolation, cryopreservation, and recovery of equine hepatocytes are presented. Furthermore, the intrinsic clearance (Clint) and production of metabolites for three drugs were compared between freshly isolated and recovered cryopreserved hepatocytes. Primary equine hepatocytes were isolated using a two-step collagenase perfusion method, with an average cell yield of 2...
October 2016: Pharmacology Research & Perspectives
Yosuke Hashimoto, Yumi Kawahigashi, Tomoyuki Hata, Xiangru Li, Akihiro Watari, Minoru Tada, Akiko Ishii-Watabe, Yoshiaki Okada, Takefumi Doi, Masayoshi Fukasawa, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
Claudin-4 (CLDN-4), a tight-junction protein, is overexpressed in various malignant tumors, including gastric, colorectal, pancreatic, and breast cancers. However, CLDN-4 is also expressed in normal tissues, including the liver, pancreas, kidney, and small intestine. Whether CLDN-4 is an effective and safe target for cancer therapy has been unclear owing to the lack of a binder with both CLDN-4 specificity and cross-reactivity to human and murine cells. In this study, we successfully generated a rat anti-CLDN-4 monoclonal antibody (5D12) that was specific to, and cross-reactive with, human and mouse CLDN-4...
October 2016: Pharmacology Research & Perspectives
Beth Williamson, Mathias Lorbeer, Michael D Mitchell, Timothy G Brayman, Robert J Riley
The nuclear pregnane X receptor (PXR) regulates the expression of genes involved in the metabolism, hepatobiliary disposition, and toxicity of drugs and endogenous compounds. PXR is a promiscuous nuclear hormone receptor (NHR) with significant ligand and DNA-binding crosstalk with the constitutive androstane receptor (CAR); hence, defining the precise role of PXR in gene regulation is challenging. Here, utilising a novel PXR-knockout (KO) HepaRG cell line, real-time PCR analysis was conducted to determine PXR involvement for a range of inducers...
October 2016: Pharmacology Research & Perspectives
Masashi Tawa, Tomio Okamura
Coronary artery disease is associated with oxidative stress due to the excessive generation of free radicals in the vascular wall. This study investigated the impact of tert-butyl hydroperoxide (t-BuOOH), a peroxyl radical generator, on the redox state of soluble guanylate cyclase (sGC) in isolated monkey coronary arteries. Helically cut strips of endothelium-intact monkey coronary arteries treated with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (10 μmol/L) were exposed for approximately 60 min to either no drug or t-BuOOH (100 μmol/L) in the presence and absence of α-tocopherol (300 μmol/L)...
October 2016: Pharmacology Research & Perspectives
Alexander M Fassmer, Edeltraut Garbe, Niklas Schmedt
The aim of this study was to analyze the population-based frequency of classic (c-) and biologic (b-) disease-modifying antirheumatic drug (DMARD) use over time, selected underlying indications and the specialty of the prescribing physicians in Germany. Based on the claims data of the German Pharmacoepidemiological Research Database (GePaRD), yearly cross-sectional studies were conducted from 2004 to 2011. The prevalence of DMARD use was calculated as the number of persons with at least one dispensation per 1000 persons stratified by sex and age...
October 2016: Pharmacology Research & Perspectives
Hui Liu, Hongjun Jin, Xuyi Yue, Junbin Han, Hao Yang, Hubert Flores, Yi Su, David Alagille, Joel S Perlmutter, Gilles Tamagnan, Zhude Tu
Phosphodiesterase 10A (PDE10A) inhibitors show therapeutic effects for diseases with striatal pathology. PET radiotracers have been developed to quantify in vivo PDE10A levels and target engagement for therapeutic interventions. The aim of this study was to compare two potent and selective PDE10A radiotracers, [(11)C]TZ1964B and [(18)F]MNI659 in the nonhuman primate (NHP) brain. Double scans in the same cynomolgus monkey on the same day were performed after injection of [(11)C]TZ1964B and [(18)F]MNI659. Specific uptake was determined in two ways: nondisplaceable binding potential (BPND) was calculated using cerebellum as the reference region and the PDE-10A enriched striatum as the target region of interest (ROI); the area under the time-activity curve (AUC) for the striatum to cerebellum ratio was also calculated...
October 2016: Pharmacology Research & Perspectives
Olufunmilayo E Adejumo, Taiwo R Kotila, Adeyinka G Falusi, Boladale O Silva, Jacinta N Nwogu, Pius S Fasinu, Chinedum P Babalola
Polymorphic expression of metabolic enzymes have been identified as one of the key factors responsible for the interindividual/ethnic/racial variability in drug metabolism and effect. In Nigeria, there is a disproportionately high incidence of sickle-cell disease (SCD), a condition characterized by painful crisis frequently triggered by malaria. Proguanil, a substrate of the polymorphic CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients in Nigeria. This study aimed to conduct a comparative CYP2C19 phenotyping among SCD patients and healthy controls and to compare the results with those previously reported...
October 2016: Pharmacology Research & Perspectives
Luca Loprete, Chiara Leuratti, Carlo Cattaneo, Mita M Thapar, Colm Farrell, Marco Sardina
Safinamide is an orally administered α-aminoamide derivative with both dopaminergic and non-dopaminergic properties. Nonlinear mixed effects models for population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PKPD) analyses were developed using records from, respectively, 623 and 668 patients belonging to two Phase 3, randomized, placebo-controlled, double-blind efficacy studies. The aim was to estimate safinamide population PK parameters in patients with Parkinson's disease (PD) on stable levodopa therapy, and to develop a model of safinamide effect on the PD phase of normal functioning (ON-time)...
October 2016: Pharmacology Research & Perspectives
Nicole E Brown, Nevin A Lambert, John R Hepler
RGS14 is a multifunctional scaffolding protein possessing two distinct G protein interaction sites including a regulator of G protein signaling (RGS) domain that acts as a GTPase activating protein (GAP) to deactivate Gαi/o-GTP proteins, and a G protein regulatory (GPR) motif that binds inactive Gαi1/3-GDP proteins independent of Gβγ. GPR interactions with Gαi recruit RGS14 to the plasma membrane to interact with Gαi-linked GPCRs and regulate Gαi signaling. While RGS14 actions on Gα proteins are well characterized, consequent effects on Gβγ signaling remain unknown...
October 2016: Pharmacology Research & Perspectives
Lisa Oezel, Hanna Then, Anna L Jung, Samir Jabari, Gabriel A Bonaterra, Thaddeus T Wissniowski, Susanne F Önel, Matthias Ocker, Kati Thieme, Ralf Kinscherf, Pietro Di Fazio
Fibromyalgia is characterized by widespread musculoskeletal pain, fatigue, and depression. The aim was to analyze potential mitochondrial dysfunction or autophagy in mice after exposure to intermittent cold stress (ICS). Muscle and liver specimens were obtained from 36 mice. Lactate dehydrogenase (LDH) activity was measured. Microtubule-associated protein light chain 3 (MAP1LC3B) and glycogen content were determined histologically; muscle ultrastructure by electron microscopy. Mitochondrial- and autophagy-related markers were analyzed by RT-qPCR and Western blotting...
October 2016: Pharmacology Research & Perspectives
Mark Soave, Leigh A Stoddart, Alastair Brown, Jeanette Woolard, Stephen J Hill
Previous research has indicated that allosteric interactions across the dimer interface of β 1-adrenoceptors may be responsible for a secondary low affinity binding conformation. Here we have investigated the potential for probe dependence, in the determination of antagonist pKi values at the human β 1-adenoceptor, which may result from such allosterism interactions. Three fluorescent β 1-adrenoceptor ligands were used to investigate this using bioluminescence energy transfer (BRET) between the receptor-bound fluorescent ligand and the N-terminal NanoLuc tag of a human β 1-adrenoceptor expressed in HEK 293 cells (NanoBRET)...
October 2016: Pharmacology Research & Perspectives
Jessica O Williams, Eddie C Y Wang, Derek Lang, Anwen S Williams
Murine collagen-induced arthritis (mCIA) is characterized by decreased vascular constriction responses and increased MMP-9. Here, we describe additional histological alterations within the aorta and surrounding perivascular adipose tissue (PVAT), study the role of PVAT in constriction response, and investigate the potential involvement of death receptor 3 (DR3). mCIA was induced in wild-type (WT) and DR3(-/-) mice with nonimmunized, age-matched controls. Vascular function was determined in isolated aortic rings ±PVAT, using isometric tension myography, in response to cumulative serotonin concentrations...
August 2016: Pharmacology Research & Perspectives
Vijayalakshmi S Pratha, Thomas McGraw, William Tobin
Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single-center, open-label, three-way crossover study, onset of action of immediate-release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR-OME) and delayed-release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR-OME, or DR-lansoprazole, or no treatment for 7 days...
June 2016: Pharmacology Research & Perspectives
Kensuke Sakuma, Chiori Yabuki, Minoru Maruyama, Akiko Abiru, Hidetoshi Komatsu, Nobuyuki Negoro, Yoshiyuki Tsujihata, Koji Takeuchi, Yugo Habata, Masaaki Mori
Fasiglifam (TAK-875) is a free fatty acid receptor 1 (FFAR1)/G-protein-coupled receptor 40 (GPR40) agonist that improves glycemic control in type 2 diabetes with minimum risk of hypoglycemia. Fasiglifam potentiates glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells glucose dependently, although the precise mechanism underlying the glucose dependency still remains unknown. Here, we investigated key cross-talk between the GSIS pathway and FFAR1 signaling, and Ca(2+) dynamics using mouse insulinoma MIN6 cells...
June 2016: Pharmacology Research & Perspectives
Ayeshah A Rosdah, Jessica K Holien, Lea M D Delbridge, Gregory J Dusting, Shiang Y Lim
Mitochondria are morphologically dynamic organelles constantly undergoing processes of fission and fusion that maintain integrity and bioenergetics of the organelle: these processes are vital for cell survival. Disruption in the balance of mitochondrial fusion and fission is thought to play a role in several pathological conditions including ischemic heart disease. Proteins involved in regulating the processes of mitochondrial fusion and fission are therefore potential targets for pharmacological therapies...
June 2016: Pharmacology Research & Perspectives
Nathalie Vernaz, Victoria Rollason, Liene Adlere, Christophe Combescure, Antoine Poncet, Pascal Bonnabry, Jules Desmeules
The antiplatelet clopidogrel and the proton pump inhibitor esomeprazole demonstrate a pharmacokinetic interaction through CYP2C19 that could translate into clinical inefficacy of clopidogrel. No medical consensus as to their coprescription has been reached, and different guidelines are available. We evaluated the prescribing practices at the Geneva University Hospitals (HUG) by measuring whether the coprescription was staggered as suggested by experts. We estimated the financial impact of different implementation guidelines...
June 2016: Pharmacology Research & Perspectives
Dominic K T Pang, Zengxuan Nong, Brian G Sutherland, Cynthia G Sawyez, Debra L Robson, Jelena Toma, J Geoffrey Pickering, Nica M Borradaile
Niacin can reduce vascular disease risk in individuals with metabolic syndrome, but in light of recent large randomized controlled trials outcomes, its biological actions and clinical utility remain controversial. Niacin can improve endothelial function, vascular inflammation, and vascular regeneration, independent of correcting dyslipidemia, in various lean rodent models of vascular injury. Here, we tested whether niacin could directly improve endothelial cell angiogenic function during combined exposure to excess fatty acids and hypoxia, and whether intervention with niacin during continued feeding of western diet could improve revascularization and functional recovery in obese, hyperlipidemic mice with peripheral ischemia...
June 2016: Pharmacology Research & Perspectives
Hiroka Suzuki, Eiji Sasaki, Ayumi Nakagawa, Yukiko Muraki, Noriyuki Hatano, Katsuhiko Muraki
The effects of diclofenac (Dic), an acetic acid derivative-type nonsteroidal anti-inflammatory drug, were examined on the function of transient receptor potential (TRP) melastatin (TRPM) 3 (TRPM3) in human embryonic kidney 293 cell-line (HEK293) cells with recombinant human TRPM3 isoforms (TRPM31325, TRPM3-3, TRPM3-9, and TRPM3-S) and in a neuroblastoma cell line human neuroblastoma IMR-32 cells (IMR-32 cells) derived from human peripheral neurons. TRPM3 responses evoked by pregnenolone sulfate (PregS) were effectively inhibited by Dic in a concentration-dependent manner in Ca(2+) measurement and electrophysiological assays...
June 2016: Pharmacology Research & Perspectives
Vitor Caiaffo, Belisa D R Oliveira, Fabrício B de Sá, Joaquim Evêncio Neto
Fluoxetine is a selective serotonin uptake inhibitor that has been widely used to determine the neurotransmission of serotonin in the central nervous system. This substance has emerged as the drug of choice for the treatment of depression due to is safer profile, fewer side effects, and greater tolerability. Studies have found the following important functions of fluoxetine related to the central nervous system: neuroprotection; anti-inflammatory properties similar to standard drugs for the treatment of inflammatory conditions; antioxidant properties, contributing to its therapeutic action and an important intracellular mechanism underlying the protective pharmacological effects seen in clinical practice in the treatment of different stress-related adverse health conditions; and antiapoptotic properties, with greater neuron survival and a reduction in apoptosis mediators as well as oxidative substances, such as superoxide dismutase and hydrogen peroxide...
June 2016: Pharmacology Research & Perspectives
Steven K Burke, David Bunton, Karen Bingham, Emma Moss, Kimberly S Bland, Barry Starcher, Marco D Wong, F Nicholas Franano
Vascular tissue contains abundant elastic fibers that contribute to vessel elasticity. Vonapanitase (formerly PRT-201) is a recombinant human chymotrypsin-like elastase family member 1 (CELA1) shown to cleave the elastin component of elastic fibers, resulting in increased vessel diameter. The purpose of these current studies was to determine vein diameter, wall thickness, elastin content, and vonapanitase potency in veins used in a model of arteriovenous fistula (AVF) and in patients undergoing AVF creation for hemodialysis access to guide dose selection for human trials...
June 2016: Pharmacology Research & Perspectives
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"