6,076,052 results match your criteria Pharmacology & Toxicology[Journal]

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CP-25 combined with MTX/ LEF ameliorates the progression of adjuvant-induced arthritis by the inhibition on GRK2 translocation.

Biomed Pharmacother 2018 Dec 14;110:834-843. Epub 2018 Dec 14.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China. Electronic address:

Objective: CP-25 attenuates arthritis progression in animal models by inhibiting G protein-coupled receptor kinase 2 (GRK2) membrane expression. This study compared groups treated with high-dose methotrexate (MTX)/leflunomide (LEF) and CP-25 combined with low-dose MTX/LEF in an adjuvant-induced arthritis (AA) rat model and investigated possible mechanisms.

Methods: AA was induced in rats via complete Freund's adjuvant. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.12.040DOI Listing
December 2018

Neuronal Receptors Display Cytoskeleton-Independent Directed Motion on the Plasma Membrane.

iScience 2018 Dec 5;10:234-244. Epub 2018 Dec 5.

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE1 1UL, UK; MRC Centre for Neurodevelopmental Disorders, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK. Electronic address:

Directed transport of transmembrane proteins is generally believed to occur via intracellular transport vesicles. However, using single-particle tracking in rat hippocampal neurons with a pH-sensitive quantum dot probe that specifically reports surface movement of receptors, we have identified a subpopulation of neuronal EphB2 receptors that exhibit directed motion between synapses within the plasma membrane itself. This receptor movement occurs independently of the cytoskeleton but is dependent on cholesterol and is regulated by neuronal activity. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S25890042183023
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http://dx.doi.org/10.1016/j.isci.2018.12.001DOI Listing
December 2018
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A mouse model for intellectual disability caused by mutations in the X-linked 2'‑O‑methyltransferase Ftsj1 gene.

Biochim Biophys Acta Mol Basis Dis 2018 Dec 14. Epub 2018 Dec 14.

Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Felix-Hausdorff-Strasse 8, 17489 Greifswald, Germany.

Mutations in the X chromosomal tRNA 2'‑O‑methyltransferase FTSJ1 cause intellectual disability (ID). Although the gene is ubiquitously expressed affected individuals present no consistent clinical features beyond ID. In order to study the pathological mechanism involved in the aetiology of FTSJ1 deficiency-related cognitive impairment, we generated and characterized an Ftsj1 deficient mouse line based on the gene trapped stem cell line RRD143. Read More

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http://dx.doi.org/10.1016/j.bbadis.2018.12.011DOI Listing
December 2018

Status of antimicrobial stewardship programs in Nigerian tertiary healthcare facilities; findings and implications.

J Glob Antimicrob Resist 2018 Dec 14. Epub 2018 Dec 14.

Division of Clinical Pharmacology, Karolinska Institute, Stockholm, Sweden; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; Health Economics Centre, Liverpool University Management School, Chatham Street, Liverpool, UK. Electronic address:

Objectives: The problem of antimicrobial resistance (AMR) is increasing worldwide with health-related and economic consequences. This is a concern in Africa, including Nigeria the most populous country in Africa, with its high rates of infectious diseases. Approaches to reducing AMR include instigating antimicrobial stewardship programs (ASPs) in hospitals. Read More

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http://dx.doi.org/10.1016/j.jgar.2018.11.025DOI Listing
December 2018

Comprehensive identification of protein disulfide bonds with pepsin/trypsin digestion, Orbitrap HCD and Spectrum Identification Machine.

J Proteomics 2018 Dec 14. Epub 2018 Dec 14.

Center for Advanced Proteomics Research and Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers University - New Jersey Medical School and Cancer Institute of New Jersey, Newark, NJ 07103, USA. Electronic address:

Disulfide bonds (SS) are post-translational modifications important for the proper folding and stabilization of many cellular proteins with therapeutic uses, including antibodies and other biologics. With budding advances of biologics and biosimilars, there is a mounting need for a robust method for accurate identification of SS. Even though several mass spectrometry methods have emerged for this task, their practical use rests on the broad effectiveness of both sample preparation methods and bioinformatics tools. Read More

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http://dx.doi.org/10.1016/j.jprot.2018.12.010DOI Listing
December 2018

Following spinal cord injury, PDE4B drives an acute, local inflammatory response and a chronic, systemic response exacerbated by gut dysbiosis and endotoxemia.

Neurobiol Dis 2018 Dec 14. Epub 2018 Dec 14.

Kentucky Spinal Cord Injury Research Center, University of Louisville, School of Medicine, 511 S. Floyd St., MDR 616, Louisville, KY 40202, USA; Department of Anatomical Science & Neurobiology, University of Louisville, School of Medicine, 511 S. Floyd St., MDR 616, Louisville, KY 40202, USA.

Emerging evidence links changes in the gut microbiome and intestinal barrier function to alterations in CNS function. We examined the role of endotoxin-responsive, cAMP-specific, Pde4 subfamily b (Pde4b) enzyme in gut dysbiosis induced neuro-inflammation and white matter loss following spinal cord injury (SCI). Using a thoracic contusion model in C57Bl/6 wild type female mice, SCI led to significant shifts in the gut bacterial community including an increase in the phylum Proteobacteria, which consists of endotoxin-harboring, gram-negative bacteria. Read More

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http://dx.doi.org/10.1016/j.nbd.2018.12.008DOI Listing
December 2018

Role of anoctamin 5, a gene associated with gnathodiaphyseal dysplasia, in osteoblast and osteoclast differentiation.

Bone 2018 Dec 14. Epub 2018 Dec 14.

Department of Pharmacology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea; Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju 61469, Republic of Korea. Electronic address:

Anoctamin 5 (Ano5) mutations are responsible for gnathodiaphyseal dysplasia, a rare skeletal syndrome. Despite the close linkage of Ano5 to bone remodeling, the molecular mechanisms underlying the role of Ano5 in bone remodeling remain unknown. In this study, we investigated whether Ano5 regulates osteoblast or osteoclast differentiation to maintain normal bone remodeling. Read More

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http://dx.doi.org/10.1016/j.bone.2018.12.010DOI Listing
December 2018

Diurnal Regulation of Sphingolipids in Blood.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Dec 14. Epub 2018 Dec 14.

Department of General Pharmacology and Toxicology, Goethe University Hospital, Frankfurt am Main, Germany.

Key homeostatic functions are regulated in a diurnal manner and a miss-alignment of such rhythms is believed to contribute to the pathophysiology of several diseases. Signaling sphingolipids (SLs) in plasma such as sphingosine 1-phosphate control lymphocytic trafficking, vascular reactivity and platelet activity, physiological functions all of which display a diurnal rhythm themselves. However, the rhythmicity of SL metabolism in plasma and its potential causes have not been sufficiently investigated so far. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.12.001DOI Listing
December 2018

The paroxysmal depolarization shift in epilepsy research.

Int J Biochem Cell Biol 2018 Dec 14. Epub 2018 Dec 14.

Center of Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, Waehringerstrasse 13a, 1090 Vienna, Austria. Electronic address:

Several shortcomings with currently available pharmacotherapy of epilepsy necessitate the search for new drug targets. Paroxysmal depolarization shifts (PDS) represent the cellular correlates of electrographic (e.g. Read More

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http://dx.doi.org/10.1016/j.biocel.2018.12.006DOI Listing
December 2018

Toxicology for Real-Life Risk Simulation - Editorial Preface to this Special Issue.

Toxicol Lett 2018 Dec 14. Epub 2018 Dec 14.

Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.

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http://dx.doi.org/10.1016/j.toxlet.2018.12.003DOI Listing
December 2018

Dioclea violacea lectin ameliorates inflammation in the temporomandibular joint of rats by suppressing intercellular adhesion molecule-1 expression.

Biochimie 2018 Dec 14. Epub 2018 Dec 14.

Faculdade São Leopoldo Mandic, Instituto de Pesquisas São Leopoldo Mandic, Área de Imunologia, Campinas, Brazil. Electronic address:

Inflammation of temporomandibular joint (TMJ) tissues are the most common cause of pain conditions associated with temporomandibular disorders (TMDs). After a tissue and/or neural damage, the inflammatory response is characterized by plasma extravasation and leukocytes infiltration in the TMJ tissues, which in turn, release inflammatory cytokines cascades responsible for inflammatory pain. Lectins are glycoproteins widely distributed in nature that may exhibit anti-inflammatory properties. Read More

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http://dx.doi.org/10.1016/j.biochi.2018.12.007DOI Listing
December 2018

Nicotine protects against manganese and iron-induced toxicity in SH-SY5Y cells: Implication for Parkinson's disease.

Neurochem Int 2018 Dec 14. Epub 2018 Dec 14.

Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA. Electronic address:

Manganese (Mn) and iron (Fe) are trace elements that are essential for proper growth and physiological functions as both play critical role in a variety of enzymatic reactions. At high concentrations, however, they can be toxic and cause neurodegenerative disorders, particularly Parkinson-like syndromes. Nicotine, on the other hand, has been shown to have neuroprotective effects against various endogenous or exogenous toxins that selectively damage the dopaminergic cells. Read More

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http://dx.doi.org/10.1016/j.neuint.2018.12.003DOI Listing
December 2018

KU-596 decreases mitochondrial superoxide and improves bioenergetics following downregulation of manganese superoxide dismutase in diabetic sensory neurons.

Exp Neurol 2018 Dec 14. Epub 2018 Dec 14.

Department of Pharmacology and Toxicology, University of Kansas, 5064 Malott Hall, 1251 Wescoe Hall Dr., Lawrence, KS 66045, USA. Electronic address:

Neuronal mitochondrial dysfunction and oxidative stress are key pathophysiologic mechanisms of diabetic peripheral neuropathy (DPN). KU-596 is a small molecule modulator of heat shock protein 90 (Hsp90) that can reverse clinically relevant measures of DPN in diabetic animal models. Mechanistically, drug efficacy requires Hsp70 and correlates with improving mitochondrial maximal respiratory capacity (MRC) and decreasing oxidative stress in diabetic sensory neurons. Read More

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http://dx.doi.org/10.1016/j.expneurol.2018.12.006DOI Listing
December 2018

Multiple modes of action of hydrophobic amines and their guanidine analogues on ASIC1a.

Eur J Pharmacol 2018 Dec 14. Epub 2018 Dec 14.

I.M.Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St.Petersburg 194223, Russia.

Hydrophobic monoamines containing only a hydrophobic/aromatic moiety and protonated amino group are a recently described class of acid-sensing ion channel (ASIC) modulators. Intensive studies have revealed a number of active compounds including endogenous amines and pharmacological agents and shown that these compounds potentiate and inhibit ASICs depending on their specific structure and on subunit composition of the target channel. The action of monoamines also depends on the application protocol, membrane voltage, conditioning and activating pH, suggesting complex mechanism(s) of the ligand-receptor interaction. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00142999183073
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http://dx.doi.org/10.1016/j.ejphar.2018.12.024DOI Listing
December 2018
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Inositol hexakisphosphate increases the size of platelet aggregates.

Biochem Pharmacol 2018 Dec 14. Epub 2018 Dec 14.

Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52 D-20246 Hamburg, Germany. Electronic address:

The inositol phosphates, InsP and InsP, have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP specifically increases platelet aggregate size. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.011DOI Listing
December 2018

Lung cancer stem cells: origin, features, maintenance mechanisms and therapeutic targeting.

Biochem Pharmacol 2018 Dec 14. Epub 2018 Dec 14.

Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address:

Lung cancer remains the leading cause of cancer-related deaths despite recent breakthroughs in immunotherapy. The widely embraced cancer stem cell (CSC) theory has also been applied for lung cancer, postulating that an often small proportion of tumor cells with stem cell properties are responsible for tumor growth, therapeutic resistance and metastasis. The identification of these CSCs and underlying molecular maintenance mechanisms is considered to be absolutely necessary for developing therapies for their riddance, hence achieving remission. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.010DOI Listing
December 2018

Interprofessional Pharmacology Podcasting in Advanced Practice Nursing Seminar.

Nurse Educ 2018 Dec 13. Epub 2018 Dec 13.

Author Affiliations: Faculty (Dr Ro), Seattle University School of Nursing, Washington; Clinical Pharmacist (Dr Villarreal), University of Washington Medical Center Department of Pharmacy, Seattle.

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http://dx.doi.org/10.1097/NNE.0000000000000636DOI Listing
December 2018

ABT-737 and erufosine combination against castration-resistant prostate cancer: a promising but cell-type specific response associated with the modulation of anti-apoptotic signaling.

Anticancer Drugs 2018 Dec 14. Epub 2018 Dec 14.

Toxicology and Chemotherapy Unit, German Cancer Research Center, Heidelberg, Germany.

A deeper understanding of the molecular basis of castration-resistant prostate cancer (CRPC) paved the way for the rational design and development of targeted therapies, which yielded promising preclinical results. However, translation of these potentially promising agents into clinics has usually failed, partly because of tumor heterogeneity. In this study, anticancer activities of the Bcl-2 inhibitor ABT-737 and the Akt-inhibitor erufosine (ErPC3) alone and in combination were compared between CRPC (PC-3 and DU-145) and healthy (PNT-1A) cell lines. Read More

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http://dx.doi.org/10.1097/CAD.0000000000000736DOI Listing
December 2018

The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM.

AIDS 2019 Feb;33(2):237-246

Division of Infectious Diseases, Weill Cornell Medicine, New York, New York.

Objective: HIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants. Read More

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http://dx.doi.org/10.1097/QAD.0000000000002038DOI Listing
February 2019

Both β-1 adrenoceptors and AT1 receptors may not be involved in the catecholamine-induced lethal arrhythmias.

Can J Physiol Pharmacol 2018 Dec 17. Epub 2018 Dec 17.

Institute of Cardiovascular Sciences , St. Boniface General Hospital Research Centre , 351 Tache Avenue , Winnipeg, Manitoba, Canada , R2H 2A6 ;

Although an excessive amount of catecholamines is known to produce arrhythmias, the exact mechanisms of this derangement are not fully understood. For this purpose, Sprague-Dawley rats were treated with or without atenolol, a -adrenoceptor blocker (20 mg/kg/day), for 15 days followed by injections of epinephrine for cumulative doses of 4 to128 µg/kg. Another group of animals was pretreated with losartan, an angiotensin receptor (AT1) blocker (20 mg/kg/day) for comparison. Read More

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http://dx.doi.org/10.1139/cjpp-2018-0531DOI Listing
December 2018

Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Intravenous Dose of Miridesap in Healthy Japanese Subjects.

Clin Pharmacol Drug Dev 2018 Dec 17. Epub 2018 Dec 17.

Medicines Development, Japan Development Division, GlaxoSmithKline K.K., Tokyo, Japan.

This phase 1 study characterized the safety, tolerability, pharmacokinetics, and pharmacodynamics of miridesap (GSK2315698) following an intravenous (IV) infusion in healthy Japanese men. Subjects in Cohort 1 received 1-hour IV infusions of 10, 20, and 40 mg of miridesap or placebo, and subjects in Cohort 2 received a 15-hour IV infusion of 20 mg/h of miridesap or placebo. No treatment-related adverse events were reported. Read More

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http://doi.wiley.com/10.1002/cpdd.631
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http://dx.doi.org/10.1002/cpdd.631DOI Listing
December 2018
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Use of proton pump inhibitors among Danish children: a 16-year register-based nationwide study.

Basic Clin Pharmacol Toxicol 2018 Dec 17. Epub 2018 Dec 17.

Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern, Denmark.

Objectives: Proton pump inhibitors (PPI) are among the most frequently used drugs in the developed countries. In recent years, their use among children and adolescents has been on the increase. Guidelines recommend use for a period no longer than 4-8 weeks. Read More

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http://dx.doi.org/10.1111/bcpt.13191DOI Listing
December 2018

Population Pharmacokinetic Study and Individual Dose Adjustments of High-Dose Methotrexate in Chinese Pediatric Patients With Acute Lymphoblastic Leukemia or Osteosarcoma.

J Clin Pharmacol 2018 Dec 17. Epub 2018 Dec 17.

School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.

High-dose methotrexate (>0.5 g/m ) is among the first-line chemotherapeutic agents used in treating acute lymphoblastic leukemia (ALL) and osteosarcoma in children. Despite rapid hydration, leucovorin rescue, and routine therapeutic drug monitoring, severe toxicity is not uncommon. Read More

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http://dx.doi.org/10.1002/jcph.1349DOI Listing
December 2018

The Safety and Effectiveness of Field Nitroglycerin in Patients with Suspected ST Elevation Myocardial Infarction.

Prehosp Emerg Care 2018 Dec 17:1-28. Epub 2018 Dec 17.

b Department of Emergency Medicine , Harbor-UCLA Medical Center and Los Angeles Biomedical Institute , Torrance , CA , USA ;

Objective: While widely used in the treatment of cardiac conditions, only limited data characterize out-of-hospital nitroglycerin (NTG) use. We sought to determine the safety of out-of-hospital sublingual NTG administered for suspected ST-segment elevation myocardial infarction (STEMI) and its effect on the patient's pain score.

Methods: We prospectively identified adult patients with suspected STEMI transported by paramedics to three PCI-capable hospitals in a large urban-suburban EMS system. Read More

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http://dx.doi.org/10.1080/10903127.2018.1558318DOI Listing
December 2018

Bevacizumab in refractory higher-grade and atypical meningioma: the current state of affairs.

Expert Opin Biol Ther 2018 Dec 17:1-6. Epub 2018 Dec 17.

e Department of Radiology and Imaging , State University of Medicine and Pharmacy "Nicolae Testemitanu" , Chisinau , Moldova.

Introduction: Historically, systemic agents had shown limited efficacy in meningioma, at the expense of significant pharmacologic and/or financial toxicity. As meningiomas are highly vascularized, they might derive benefit from antiangiogenic therapy. Areas covered: This review summarizes the literature regarding bevacizumab pharmacology, safety and efficacy in patients with refractory meningioma. Read More

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http://dx.doi.org/10.1080/14712598.2019.1559292DOI Listing
December 2018

UCP2 Overexpression Redirects Glucose into Anabolic Metabolic Pathways.

Proteomics 2018 Dec 17:e1800353. Epub 2018 Dec 17.

Department of Pharmacology, Toxicology & Neuroscience, LSU Health Sciences Center, Shreveport, LA, 71130.

Uncoupling protein 2 (UCP2) is often upregulated in cancer cells. The UCP2 upregulation is positively correlated with enhanced proliferation, tumorigenesis, and metabolic alterations, thus suggesting that UCP2 upregulation could play a key role in sensing metabolic changes to promote tumorigenesis. To determine the global metabolic impact of UCP2 upregulation, we used C glucose as a source molecule to 'trace' the metabolic fate of carbon atoms derived from glucose. Read More

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http://dx.doi.org/10.1002/pmic.201800353DOI Listing
December 2018
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Overview of the blood compatibility of nanomedicines: A trend analysis of in vitro and in vivo studies.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2018 Dec 17:e1546. Epub 2018 Dec 17.

Consumer Products Safety Unit, Directorate F - Health, Consumers and Reference Materials, European Commission Joint Research Centre (JRC), Ispra (VA), Italy.

As nanomedicines have the potential to address many currently unmet medical needs, the early identification of regulatory requirements that could hamper a smooth translation of nanomedicines from the laboratory environment to clinical applications is of utmost importance. The blood system is especially relevant as many nanomedicinal products that are currently under development are designed for intravenous administration and cells of the blood system will be among the first biological systems exposed to the injected nanomedicine. This review collects and summarizes the current knowledge related to the blood compatibility of nanomedicines and nanomaterials with a potential use in biomedical applications. Read More

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http://dx.doi.org/10.1002/wnan.1546DOI Listing
December 2018

Flow Cytometry Analysis of Free Intracellular NAD Using a Targeted Biosensor.

Curr Protoc Cytom 2018 Dec 17:e54. Epub 2018 Dec 17.

Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas.

Flow cytometry approaches combined with a genetically encoded targeted fluorescent biosensor are used to determine the subcellular compartmental availability of the oxidized form of nicotinamide adenine dinucleotide (NAD ). The availability of free NAD can affect the activities of NAD -consuming enzymes such as sirtuin, PARP/ARTD, and cyclic ADPR-hydrolase family members. Many methods for measuring the NAD available to these enzymes are limited because they cannot determine free NAD as it exists in various subcellular compartments distinctly from bound NAD or NADH. Read More

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http://dx.doi.org/10.1002/cpcy.54DOI Listing
December 2018

An alternative approach to relapse analysis: using Monte Carlo methods and proportional rates of response.

J Exp Anal Behav 2018 Dec 17. Epub 2018 Dec 17.

Utah State University.

Relapse is the recovery of a previously suppressed response. Animal models have been useful in examining the mechanisms underlying relapse (e.g. Read More

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http://dx.doi.org/10.1002/jeab.489DOI Listing
December 2018

Selective MMP-13 inhibitors: promising agents for the therapy of Osteoarthritis.

Curr Med Chem 2018 Dec 17. Epub 2018 Dec 17.

Key Laboratory of Theoretical Organic Chemistry and Functional Molecule, Ministry of Education, Hunan Provincial Key Laboratory of Controllable Preparation and Functional Application of Fine Polymers, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, Hunan 411201. China.

Osteoarthritis (OA) is an age-related degenerative disease, which is characterized by the chronic joint pain, inflammation and the damage of joint cartilage. At present, steroidal drugs and nonsteroidal anti-inflammatory drugs (NSAIDS), selective cyclooxygenase-2 (COX-2) inhibitors, are the first-line drugs for the treatment of OA. However, these drugs could lead to some cardiovascular side effects. Read More

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http://dx.doi.org/10.2174/0929867326666181217153118DOI Listing
December 2018

Joshua Harold Burn (1892-1981): A visionary during the evolution of pharmacology as a biomedical discipline.

Authors:
Ronald P Rubin

J Med Biogr 2018 Dec 17:967772016685908. Epub 2018 Dec 17.

Department of Pharmacology and Toxicology, Jacobs School of Medicine, the State University of New York at Buffalo, Buffalo, NY, USA.

This article encapsulates the career of Joshua Burn, whose work encouraged new lines of experimentation and paved the way for fundamental advances in our knowledge of the autonomic nervous system. His legacy also endures in his efforts as Department Chairman to oversee a very supportive environment which led to the development of many successful scientists. By producing a body of work that enabled the discipline of pharmacology to contribute in a major way to the advancement of clinical medicine, Joshua Burn stands out as a unique figure in the annals of true scientific pioneers. Read More

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http://dx.doi.org/10.1177/0967772016685908DOI Listing
December 2018

Packaging functionally-important plasma proteins into the α-granules of human induced pluripotent stem cell-derived megakaryocytes.

J Tissue Eng Regen Med 2018 Dec 17. Epub 2018 Dec 17.

Blood Center of Wisconsin, Blood Research Institute, Milwaukee, WI.

The contents of platelet α-granules arrive via a number of pathways; some are synthesized by megakaryocytes (MKs), e.g., von Willebrand Factor (VWF), while others are endocytosed from plasma, e. Read More

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http://dx.doi.org/10.1002/term.2785DOI Listing
December 2018

A recurrent mutation in KCNQ4 in Korean families with nonsyndromic hearing loss and rescue of the channel activity by KCNQ activators.

Hum Mutat 2018 Dec 17. Epub 2018 Dec 17.

Department of Pharmacology, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, 03722, Korea.

Mutations in potassium voltage-gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to nonsyndromic hearing loss (NSHL), deafness nonsyndromic autosomal dominant 2 (DFNA2). To identify causative mutations of hearing loss in 98 Korean families, we performed whole exome sequencing. In three independent families with NSHL, we identified a cosegregating heterozygous missense mutation, c. Read More

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http://dx.doi.org/10.1002/humu.23698DOI Listing
December 2018

The novel protective effects of loganin against 1-methyl-4-phenylpyridinium-induced neurotoxicity: Enhancement of neurotrophic signaling, activation of IGF-1R/GLP-1R, and inhibition of RhoA/ROCK pathway.

Phytother Res 2018 Dec 16. Epub 2018 Dec 16.

Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Loganin, a major iridoid glycoside obtained from fruits of Cornus officinalis, possesses anti-inflammatory, antitumor, antidiabetic, and osteoporosis prevention effects. Loganin has been linked to neuroprotection in several models of neurodegeneration, including Parkinson's disease (PD). However, mechanisms underlying the neuroprotective effects of loganin are still mostly unknown. Read More

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http://dx.doi.org/10.1002/ptr.6259DOI Listing
December 2018

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.

Phytother Res 2018 Dec 16. Epub 2018 Dec 16.

Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000, Novi Sad, Serbia.

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. Read More

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http://dx.doi.org/10.1002/ptr.6251DOI Listing
December 2018

Population Pharmacokinetics of the BTK Inhibitor Acalabrutinib and its Active Metabolite in Healthy Volunteers and Patients with B-Cell Malignancies.

Clin Pharmacokinet 2018 Dec 17. Epub 2018 Dec 17.

Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Boston, MA, USA.

Introduction: Bruton tyrosine kinase (BTK) is a key component of B-cell receptor signalling, critical for cell proliferation. Acalabrutinib, a selective, covalent BTK inhibitor, recently received an accelerated approval in relapsed/refractory mantle cell lymphoma. This analysis characterized the population pharmacokinetics (PK) of acalabrutinib and its metabolite ACP-5862. Read More

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http://dx.doi.org/10.1007/s40262-018-0725-7DOI Listing
December 2018

Cannabinoid CB Receptor Antagonist Rimonabant Decreases Levels of Markers of Organ Dysfunction and Alters Vascular Reactivity in Aortic Vessels in Late Sepsis in Rats.

Inflammation 2018 Dec 17. Epub 2018 Dec 17.

Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, Curitiba, Paraná, Brazil.

Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. Read More

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http://dx.doi.org/10.1007/s10753-018-0919-zDOI Listing
December 2018

Perinatal Nutritional Reprogramming of the Epigenome Promotes Subsequent Development of Nonalcoholic Steatohepatitis.

Hepatol Commun 2018 Dec 1;2(12):1493-1512. Epub 2018 Oct 1.

Division of Pediatric Gastroenterology and Hepatology Mayo Clinic Rochester MN.

With the epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common pediatric liver disease. The influence of a perinatal obesity-inducing diet (OID) on the development and progression of NAFLD in offspring is important but incompletely studied. Hence, we fed breeding pairs of C57BL/6J mice during gestation and lactation (perinatally) either chow or an OID rich in fat, fructose, and cholesterol (FFC). Read More

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http://dx.doi.org/10.1002/hep4.1265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287484PMC
December 2018

Hemp ( L.) Seed Phenylpropionamides Composition and Effects on Memory Dysfunction and Biomarkers of Neuroinflammation Induced by Lipopolysaccharide in Mice.

ACS Omega 2018 Nov 27;3(11):15988-15995. Epub 2018 Nov 27.

Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences and Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.

Hempseed has achieved a growing popularity in human nutrition, particularly regarding essential amino acids and fatty acids. The multiple positive attributes of hempseed have led to the further study of its constituents. In this study, hempseed extract containing phenylpropionamides (TPA) was obtained and its chemical profile and content were obtained using high-performance liquid chromatography technology based on previous study. Read More

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http://dx.doi.org/10.1021/acsomega.8b02250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288804PMC
November 2018

Na-Montmorillonite-Dispersed Sustainable Polymer Nanocomposite Hydrogel Films for Anticancer Drug Delivery.

ACS Omega 2018 Nov 20;3(11):15809-15820. Epub 2018 Nov 20.

Material Research Laboratory, Department of Chemistry and Genome Biology Lab, Department of Biosciences, Jamia Millia Islamia, New Delhi 110025, India.

Nanocomposite hydrogels have found a wide scope in regenerative medicine, tissue engineering, and smart drug delivery applications. The present study reports the formulations of biocompatible nanocomposite hydrogel films using carboxymethyl cellulose-hydroxyethyl cellulose-acrylonitrile-linseed oil polyol (CHAP) plain hydrogel and Na-montmorillonite (NaMMT) dispersed CHAP nanocomposite hydrogel films (NaCHAP) using solution blending technique. The structural, morphological, and mechanical properties of resultant nanocomposite hydrogel films were further investigated to analyze the effects of polyol and NaMMT on the characteristic properties. Read More

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http://dx.doi.org/10.1021/acsomega.8b01691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288778PMC
November 2018

Quantitative Interrelation between Atractylenolide I, II, and III in Koidzumi Rhizomes, and Evaluation of Their Oxidative Transformation Using a Biomimetic Kinetic Model.

ACS Omega 2018 Nov 5;3(11):14833-14840. Epub 2018 Nov 5.

Department of Chemistry, The Research Institute of Natural Sciences, Sookmyung Women's University, 04310 Seoul, Republic of Korea.

Analytical methods based on ultraperformance liquid chromatography/ion-trap mass spectrometry (UPLC/ion-trap MS) were developed for quantification of atractylenolide I, II, and III in the methanol extract of rhizomes with a C column in an acidified water/acetonitrile gradient eluent in an LC system, and ion-trap MS coupled with electrospray ionization was employed under positive-ion mode. The three atractylenolides were quantified in all samples, and the content of atractylenolide I, II, and III showed a significant correlation to each other. Such high correlation was explained by the mechanistic insights into the biosynthetic pathway of atractylenoide III and I from atractylenoide II by using the biomimetic cytochrome P450 model, [Fe(tmp)](CFSO) (tmp = -tetramesitylporphyrin). Read More

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http://dx.doi.org/10.1021/acsomega.8b02005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289488PMC
November 2018

Label-Free Whole Cell Biosensing for High-Throughput Discovery of Activators and Inhibitors Targeting G Protein-Activated Inwardly Rectifying Potassium Channels.

ACS Omega 2018 Nov 5;3(11):14814-14823. Epub 2018 Nov 5.

Molecular, Cellular and Pharmacobiology Section, Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn, Germany.

Dynamic mass redistribution (DMR) and cellular dielectric spectroscopy (CDS) are label-free biosensor technologies that capture real-time integrated cellular responses upon exposure to extra- and intracellular stimuli. They register signaling routes that are accompanied by cell shape changes and/or molecular movement of cells proximal to the biosensor to which they are attached. Here, we report the unexpected observation that robust DMR and CDS signatures are also elicited upon direct stimulation of G protein-activated inwardly rectifying potassium (GIRK) channels, which are involved in the regulation of excitability in the heart and brain. Read More

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http://dx.doi.org/10.1021/acsomega.8b02254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289404PMC
November 2018

Toxic cutaneous responses from inhalant abuse.

JAAD Case Rep 2019 Jan 4;5(1):31-33. Epub 2018 Dec 4.

Department of Dermatology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio.

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http://dx.doi.org/10.1016/j.jdcr.2018.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280677PMC
January 2019

Spindle Checkpoint Regulators in Insulin Signaling.

Front Cell Dev Biol 2018 29;6:161. Epub 2018 Nov 29.

Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States.

The spindle checkpoint ensures accurate chromosome segregation during mitosis and guards against aneuploidy. Insulin signaling governs metabolic homeostasis and cell growth, and its dysregulation leads to metabolic disorders, such as diabetes. These critical pathways have been extensively investigated, but a link between the two has not been established until recently. Read More

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http://dx.doi.org/10.3389/fcell.2018.00161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281718PMC
November 2018

Multiple mechanisms involved in a low concentration of FL118 enhancement of AMR-MeOAc to induce pancreatic cancer cell apoptosis and growth inhibition.

Am J Cancer Res 2018 1;8(11):2267-2283. Epub 2018 Nov 1.

Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center Buffalo, NY 14263, USA.

Activating mutations in GTPase protein KRAS occurs in approximately 90% of pancreatic cancers. Mutated KRAS lead to constitutive activation of RAF/MEK/ERK and PI3K/Akt pathways in pancreatic cancer. There is currently no effective KRAS-targeted therapeutics available in the clinic for treating this subset of cancer. Read More

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November 2018

Using a cross-contextual reciprocal learning approach in a multisite implementation research project to improve self-management for type 2 diabetes.

BMJ Glob Health 2018 26;3(6):e001068. Epub 2018 Nov 26.

Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.

This paper reports on the use of reciprocal learning for identifying, adopting and adapting a type 2 diabetes self-management support intervention in a multisite implementation trial conducted in a rural setting in a low-income country (Uganda), a periurban township in a middle-income country (South Africa) and socioeconomically disadvantaged suburbs in a high-income country (Sweden). The learning process was guided by a framework for knowledge translation and structured into three learning cycles, allowing for a balance between evidence, stakeholder interaction and contextual adaptation. Key factors included commitment, common goals, leadership and partnerships. Read More

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http://dx.doi.org/10.1136/bmjgh-2018-001068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267315PMC
November 2018

Effects of body protection vests and experience levels in prevention of equestrian injuries.

BMJ Open Sport Exerc Med 2018 16;4(1):e000426. Epub 2018 Nov 16.

United States Pony Clubs, Lexington, Kentucky, USA.

Objectives: To investigate the risk reduction and benefit of wearing body protection/safety vests in equestrian sports.

Methods: A comparison of equestrians wearing body protective vests and those not wearing vests was performed using incident report data of 718 participants in the United States Pony Clubs during 2011-2017. Data obtained included age, gender, certification level of member, type of activity, description of incident, description of injuries, what protective equipment was worn and other possible contributing factors. Read More

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http://bmjopensem.bmj.com/lookup/doi/10.1136/bmjsem-2018-000
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http://dx.doi.org/10.1136/bmjsem-2018-000426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267465PMC
November 2018
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Economic analysis of palonosetron versus granisetron in the standard triplet regimen for preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Japan (TRIPLE phase III trial).

J Pharm Health Care Sci 2018 10;4:31. Epub 2018 Dec 10.

1Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan.

Background: We conducted an economic assessment using test data from the phase III TRIPLE study, which examined the efficacy of a 5-hydroxytryptamine 3 receptor antagonist as part of a standard triplet antiemetic regimen including aprepitant and dexamethasone in preventing chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC).

Methods: We retrospectively investigated all medicines prescribed for antiemetic purposes within 120 h after the initiation of cisplatin administration during hospitalization. In the TRIPLE study, patients were assigned to treatment with granisetron (GRA) 1 mg ( = 413) or palonosetron (PALO) 0. Read More

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http://dx.doi.org/10.1186/s40780-018-0128-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287343PMC
December 2018

Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?

Theranostics 2018 10;8(20):5784-5800. Epub 2018 Nov 10.

Department of Pharmacology, College of Medicine, The Pennsylvania State University, Hershey, PA, USA.

The last decade has witnessed significant advances in the adoptive cell transfer (ACT) technique, which has been appreciated as one of the most promising treatments for patients with cancer. Utilization of ACT can enhance the function of the immune system or improve the specificity and persistence of transferred cells. Various immune cells including T lymphocytes, natural killer cells, dendritic cells, and even stem cells can be used in the ACT despite their different functional mechanisms. Read More

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http://dx.doi.org/10.7150/thno.29035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276301PMC
November 2018

Caffeine Protects Skin from Oxidative Stress-Induced Senescence through the Activation of Autophagy.

Theranostics 2018 10;8(20):5713-5730. Epub 2018 Nov 10.

Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China.

Skin cells are vulnerable to oxidative stress-induced senescence, which may lead to abnormal aging or aging-related disorders. Therefore, strategies that can ameliorate oxidative stress-induced senescence are expected to protect skin from damage, holding the promise of treating skin diseases in the clinic. This study aims to investigate whether caffeine, a well-known purine alkaloid, is able to prevent skin from oxidative stress-induced senescence, and to explore the underlying molecular mechanisms. Read More

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http://dx.doi.org/10.7150/thno.28778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276298PMC
November 2018
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