6,129,201 results match your criteria Pharmacology Biochemistry and Behavior[Journal]

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Comparative Evaluation of Median Versus Youden Index Dichotomization Methods: Exposure-Response Analysis of Mycophenolic Acid and Acyl-Glucuronide Metabolite.

Eur J Drug Metab Pharmacokinet 2019 Mar 16. Epub 2019 Mar 16.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.

Background And Objectives: Dichotomization of pharmacokinetic exposure measures in exposure-response relationship studies provides results that are interpretable in clinical care. Several methods exist in the literature on how to define the cut-off values needed for the dichotomization process. Commonly, the sample median is utilized to define the dichotomizing value; however, statistical methods based on the exposure metric and its association with the outcome are argued to result in a more proper definition of the optimal cut-point. Read More

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http://dx.doi.org/10.1007/s13318-019-00550-2DOI Listing

Therapeutic Prospective of a Spore-Forming Probiotic-Bacillus clausii UBBC07 Against Acetaminophen-Induced Uremia in Rats.

Probiotics Antimicrob Proteins 2019 Mar 16. Epub 2019 Mar 16.

Department of Pharmacology, SSR College of Pharmacy, Silvassa, U. T. of Dadra Nagar & Haveli, 396230, India.

To screen Bacillus clausii UBBC07 as a putative probiotic strain and to examine the protective effect of probiotic-B. clausii UBBC07 spore on uremia on rats induced by acetaminophen. In vitro tests performed to screen potential probiotic strains were gastric and bile acid resistance and ability to reduce pathogen adhesion to surfaces. Read More

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http://dx.doi.org/10.1007/s12602-019-09540-xDOI Listing

An evaluation of the role of practice pharmacists in Australia: a mixed methods study.

Int J Clin Pharm 2019 Mar 16. Epub 2019 Mar 16.

Gold Coast Health, Queensland Health, Brisbane, QLD, Australia.

Background The need for greater collaboration between pharmacists and general practitioners in Australia facilitated the development of the practice pharmacist role. Practice pharmacists work from within general practices to provide services to patients and health professionals to improve the quality use of medications. Objective To explore the perceptions of Australian accredited pharmacists and pharmacists already working in general practices about current roles, facilitators and barriers, and remuneration expectations of practice pharmacists. Read More

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http://dx.doi.org/10.1007/s11096-019-00807-5DOI Listing

Effects of NOP-Related Ligands in Nonhuman Primates.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Read More

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http://dx.doi.org/10.1007/164_2019_211DOI Listing

Narcotic-Sparing Approaches and the Shift Toward Paracetamol in Neonatal Intensive Care.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Effective analgesia in neonates is relevant not only because of ethical aspects or empathy, but it is a crucial and integral part of medical and nursing care. However, there is also emerging evidence - although mainly in animal models - on the relation between the exposure to narcotics and impaired neurodevelopmental outcome, resulting in a CATCH-22 scenario. Consequently, a balanced approach is needed with the overarching intention to attain adequate pain management with minimal side effects. Read More

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http://dx.doi.org/10.1007/164_2019_207DOI Listing

Understanding CGRP and Cardiovascular Risk.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

Increasing knowledge about the role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology has led to the development of antibodies against this peptide or its receptor. However, CGRP is widely expressed throughout the body, participating not only in pathophysiological conditions but also in several physiological processes and homeostatic responses during pathophysiological events. Therefore, in this chapter, the risks of long-term blockade of the CGRP pathway will be discussed, with focus on the cardiovascular system, as this peptide has been described to have a protective role during ischemic events, and migraine patients present a higher risk of stroke and myocardial infarction. Read More

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http://dx.doi.org/10.1007/164_2019_204DOI Listing

Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.

Cell Mol Life Sci 2019 Mar 16. Epub 2019 Mar 16.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.

The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. Read More

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http://dx.doi.org/10.1007/s00018-019-03053-0DOI Listing

Comment on: A novel glucocorticoid-free maintenance regimen for anti-neutrophil cytoplasm antibody-associated vasculitis.

Rheumatology (Oxford) 2019 Mar 16. Epub 2019 Mar 16.

Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.

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http://dx.doi.org/10.1093/rheumatology/kez036DOI Listing

Selective D and D receptor antagonists oppositely modulate cocaine responses in mice via distinct postsynaptic mechanisms in nucleus accumbens.

Neuropsychopharmacology 2019 Mar 16. Epub 2019 Mar 16.

Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30322, USA.

The dopamine D receptor (DR) has emerged as a promising pharmacotherapeutic target for the treatment of several diseases including schizophrenia, Parkinson's disease, and substance use disorders. However, studies investigating the DR's precise role in dopamine neurotransmission or how it may be exploited to modulate responses to drugs of abuse have produced contrasting results, in part because most DR-targeted compounds often also interact with D receptors (DR). To resolve this issue, we set out to systematically characterize and compare the consequences of selective DR or DR antagonists on the behavioral-stimulant properties of cocaine in mice, and to identify putative neurobiological mechanisms underlying their behavior-modifying effects. Read More

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http://dx.doi.org/10.1038/s41386-019-0371-2DOI Listing

Critical appraisal of adverse effects reporting in the 'Treatment for Adolescents With Depression Study (TADS)'.

BMJ Open 2019 Mar 15;9(3):e026089. Epub 2019 Mar 15.

Department of Pharmacology, University of Oslo, Oslo, Norway.

Objective: To identify all publications from the 'Treatment for Adolescents With Depression Study (TADS)' and assess the findings regarding occurrence of any adverse effects in the treatment groups both for the short-term and long-term study stages.

Design: Descriptive analysis of TADS publications with any information on adverse effects.

Results: We identified 48 publications describing various aspects of the TADS, in which 439 adolescent patients received treatment with fluoxetine, cognitive-behavioural therapy, cognitive-behavioural therapy plus fluoxetine or placebo. Read More

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http://dx.doi.org/10.1136/bmjopen-2018-026089DOI Listing

Morphine in acute coronary syndrome: systematic review and meta-analysis.

BMJ Open 2019 Mar 15;9(3):e025232. Epub 2019 Mar 15.

Laboratory of Clinical Pharmacology and Therapeutics, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Objective: Morphine is frequently used in acute coronary syndrome (ACS) due to its analgesic effect, it being recommended in the main cardiology guidelines in Europe and the USA. However, controversy exists regarding its routine use due to potential safety concerns. We conducted a systematic review of randomised-controlled trials (RCTs) and observational studies to synthesise the available evidence. Read More

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http://dx.doi.org/10.1136/bmjopen-2018-025232DOI Listing

Novel aryl carboximidamide and 3-aryl-1,2,4-oxadiazole analogues of naproxen as dual selective COX-2/15-LOX inhibitors: Design, synthesis and docking studies.

Bioorg Chem 2019 Feb 20;85:577-584. Epub 2019 Feb 20.

Pharmacology Department, College of Pharmacy, Jouf University, Sakaka, Aljouf 2014, Saudi Arabia; Biochemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt.

A series of novel naproxen analogues containing 3-aryl-1,2,4-oxadiazoles moiety (4b-g) and their reaction intermediates aryl carboximidamides moiety (3b-g) was synthesized and evaluated in vitro as dual COXs/15-LOX inhibitors. Compounds 3b-g exhibited superior inhibitory activity than celecoxib as COX-2 inhibitors. Compounds 3b-d and 3g were the most potent COX-2 inhibitors with IC range of 6. Read More

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http://dx.doi.org/10.1016/j.bioorg.2019.02.043DOI Listing
February 2019

The in vitro and in vivo anti-inflammatory effect of osthole, the major natural coumarin from Cnidium monnieri (L.) Cuss, via the blocking of the activation of the NF-κB and MAPK/p38 pathways.

Phytomedicine 2019 Feb 18;58:152864. Epub 2019 Feb 18.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 30 Qingquan Road of Laishan District, Yantai 264003, Shandong, PR China. Electronic address:

Background: Ulcerative colitis (UC) is a chronic inflammatory condition of the intestines and is difficult to cure once diagnosed. The efficacy of the current clinical treatment for UC is limited. Common anti-inflammatory drugs are prone to adverse effects, while novel biological agents are expensive, although tolerated by patients. Read More

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http://dx.doi.org/10.1016/j.phymed.2019.152864DOI Listing
February 2019

Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation.

Colloids Surf B Biointerfaces 2019 Mar 1;178:307-316. Epub 2019 Mar 1.

Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Solid lipid nanoparticle (SLN) is a promising approach for delivery of various drugs including proteins and peptides. However, the loading of hydrophilic drugs into the lipoid matrix of SLNs is challenging. The statistical design is a potential method facilitating the optimization of nanoparticles characteristics. Read More

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http://dx.doi.org/10.1016/j.colsurfb.2019.01.027DOI Listing

Role of the P2X4 receptor in neuropathic pain.

Authors:
Kazuhide Inoue

Curr Opin Pharmacol 2019 Mar 14;47:33-39. Epub 2019 Mar 14.

Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address:

Neuropathic pain is the most important type of chronic pain because it is refractory to available medications. Neuropathic pain occurs after peripheral nerve injury (PNI) or nerve damage by various reasons. In recent decades, a growing body of evidence shows that spinal microglia and P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, play a principal role in evoking this pain. Read More

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http://dx.doi.org/10.1016/j.coph.2019.02.001DOI Listing

Peptidylarginine Deiminase Inhibitor Cl-amidine Attenuates Cornification and Interferes with the Regulation of Autophagy in Reconstructed Human Epidermis.

J Invest Dermatol 2019 Mar 13. Epub 2019 Mar 13.

UDEAR, Institut National de la Santé Et de la Recherche Médicale, Université de Toulouse Midi-Pyrénées, Toulouse, France. Electronic address:

Deimination, a post-translational modification catalyzed by a family of enzymes called peptidylarginine deiminases (PADs), is the conversion of arginine into citrulline residues in a protein. Deimination has been associated with numerous physiological and pathological processes. Our aim was to study its implication in the homeostasis of human epidermis, where three PADs are expressed, namely PAD1, 2 and 3. Read More

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http://dx.doi.org/10.1016/j.jid.2019.02.026DOI Listing

Punicalagin attenuates endothelial dysfunction by activating FoxO1, a pivotal regulating switch of mitochondrial biogenesis.

Free Radic Biol Med 2019 Mar 13. Epub 2019 Mar 13.

Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

Accumulating evidence has elucidated that hyperlipidemia is closely associated with an increasing prevalence of CVDs (cardiovascular diseases) because of endothelial dysfunction. In the present study, we investigated the effect and mechanism of PU (Punicalagin), a major ellagitannin in pomegranate, on endothelial dysfunction both in vivo and in vitro. In vivo, PU significantly ameliorated hyperlipidemia-induced accumulation of serum triglyceride and cholesterol as well as endothelial and mitochondrial dysfunction of thoracic aorta. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2019.03.011DOI Listing

Regional hypometabolism in the 3xTg mouse model of Alzheimer's disease.

Neurobiol Dis 2019 Mar 13. Epub 2019 Mar 13.

St. Boniface Hospital Research, Canada; Dept. of Pharmacology & Therapeutics, University of Manitoba, Canada. Electronic address:

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease. Although neurofibrillary tangles and amyloid beta are classic hallmarks of AD, the earliest deficits in AD progression may be caused by unknown factors. One suspected factor has to do with brain energy metabolism. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.03.008DOI Listing
March 2019
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Microglia Specific Metabolic Changes in Neurodegeneration.

Authors:
Blanca I Aldana

J Mol Biol 2019 Mar 13. Epub 2019 Mar 13.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences. University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. Electronic address:

The high energetic demand of the brain deems this organ rather sensitive to changes in energy supply. Therefore, even minor alterations in energy metabolism may underlie detrimental disturbances in brain function, contributing to the generation and progression of neurodegenerative diseases. Considerable evidence supports the key role of deficits in cerebral energy metabolism, particularly hypometabolism of glucose and mitochondrial dysfunction, in the pathophysiology of brain disorders. Read More

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http://dx.doi.org/10.1016/j.jmb.2019.03.006DOI Listing

Lactate-Mediated Protection of Retinal Ganglion Cells.

J Mol Biol 2019 Mar 13. Epub 2019 Mar 13.

Department of Drug Design and Pharmacology, University of Copenhagen, Denmark; Department of Ophthalmology, Rigshospitalet-, Glostrup, Denmark. Electronic address:

Loss of retinal ganglion cells (RGCs) is a leading cause of blinding conditions. The purpose of this study was to evaluate the effect of extracellular L-lactate on RGC survival facilitated through lactate metabolism and ATP production. We identified lactate as a preferred energy substrate over glucose in murine RGCs, and showed that lactate metabolism and consequently increased ATP production are crucial components in promoting RGC survival during energetic crisis. Read More

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http://dx.doi.org/10.1016/j.jmb.2019.03.005DOI Listing

Ccne1 Overexpression Causes Chromosome Instability in Liver Cells and Liver Tumor Development in Mice.

Gastroenterology 2019 Mar 13. Epub 2019 Mar 13.

Department of Biochemistry and Molecular Biology; Department of Pediatric and Adolescent Medicine; Department of Pediatrics. Electronic address:

Background & Aims: The CCNE1 locus, which encodes cyclin E1, is amplified in many types of cancer cells and is activated in hepatocellular carcinomas (HCCs) from patients infected with hepatitis B virus or adeno-associated virus type 2, due to integration of the virus nearby. We investigated cell cycle and oncogenic effects of cyclin E1 overexpression in tissues of mice.

Methods: We generated mice with doxycycline-inducible expression of Ccne1 (Ccne1 mice) and activated overexpression of cyclin E1 from age 3 weeks onwards. Read More

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http://dx.doi.org/10.1053/j.gastro.2019.03.016DOI Listing

Functional characterization of ABCC9 variants identified in sudden unexpected natural death.

Forensic Sci Int 2019 Feb 27;298:80-87. Epub 2019 Feb 27.

Departments of Pediatrics, NYU School of Medicine, New York, NY 10016 USA; Departments of Physiology & Neuroscience NYU School of Medicine, New York, NY 10016 USA; Departments of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY 10016 USA. Electronic address:

Background: Genetic variation in ion channel genes ('channelopathies') are often associated with inherited arrhythmias and sudden death. Genetic testing ('molecular autopsies') of channelopathy genes can be used to assist in determining the likely causes of sudden unexpected death. However, different in silico approaches can yield conflicting pathogenicity predictions and assessing their impact on ion channel function can assist in this regard. Read More

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http://dx.doi.org/10.1016/j.forsciint.2019.02.035DOI Listing
February 2019

Cannabis resin in the region of Madrid: Adulteration and contamination.

Forensic Sci Int 2019 Mar 5;298:34-38. Epub 2019 Mar 5.

Department of Anatomy and Embryology, Departmental Section in Veterinary School, Complutense University of Madrid. Avda. Puerta de Hierro s/n, 28040, Madrid, Spain. Electronic address:

The aim of this study is to analyze the adulteration and contamination of cannabis resin obtained on the streets of Madrid, in order to establish whether it is suitable for human consumption. A total of 90 samples obtained through street vending in the Region of Madrid (CAM) were analyzed. Our results showed a direct relationship between the shape of the samples (acorn or ingot) and the presence of foreign elements, adulterants and microbiological contamination. Read More

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http://dx.doi.org/10.1016/j.forsciint.2019.02.049DOI Listing

SGL5213, a novel and potent intestinal SGLT1 inhibitor, suppresses intestinal glucose absorption and enhances plasma GLP-1 and GLP-2 secretion in rats.

Eur J Pharmacol 2019 Mar 13. Epub 2019 Mar 13.

Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan. Electronic address:

Sodium-glucose cotransporter 1 (SGLT1) is the primary transporter for glucose absorption from digested nutrients in the gastrointestinal tract. Intestinal SGLT1 inhibition reduces post-prandial hyperglycemia and enhances the increase of plasma glucagon-like peptide-1 (GLP-1) levels. SGL5213 is a novel and potent intestinal SGLT1 inhibitor. Read More

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http://dx.doi.org/10.1016/j.ejphar.2019.03.023DOI Listing

Reply to: Optic nerve sheath diameter measurement in hypoxic ischaemic brain injury after cardiac arrest.

Resuscitation 2019 Mar 13. Epub 2019 Mar 13.

Division of Critical Care Medicine, Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.

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http://dx.doi.org/10.1016/j.resuscitation.2019.02.046DOI Listing

Single prolonged stress PTSD model triggers progressive severity of anxiety, altered gene expression in locus coeruleus and hypothalamus and effected sensitivity to NPY.

Eur Neuropsychopharmacol 2019 Mar 13. Epub 2019 Mar 13.

Department of Biochemistry and Molecular Biology, New York Medical College Valhalla, Basic Sciences Building, New York, NY 10595, USA. Electronic address:

PTSD is heterogeneous disorder that can be long lasting and often has delayed onset following exposure to a traumatic event. Therefore, it is important to take a staging approach to evaluate progression of biological mechanisms of the disease. Here, we begin to evaluate the temporal trajectory of changes following exposure to traumatic stressors in the SPS rat PTSD model. Read More

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http://dx.doi.org/10.1016/j.euroneuro.2019.02.010DOI Listing

GABA but not GABA receptors in the lateral hypothalamus modulate the tachycardic response to emotional stress in rats.

Eur Neuropsychopharmacol 2019 Mar 13. Epub 2019 Mar 13.

Laboratory of Pharmacology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Rodovia Araraquara-Jau Km 01 (Campus Universitário), Campus Ville, 14800-903 Araraquara, SP, Brazil; Joint UFSCar-UNESP Graduate Program in Physiological Sciences, São Carlos, SP, Brazil. Electronic address:

The lateral hypothalamus (LH) has been described as one of the hypothalamic areas involved in the behavioral and physiological responses triggered by aversive stimuli. Previous studies indicated involvement of the LH in cardiovascular responses to stress. Despite this evidence, the local neurochemical mechanisms involved in LH control of stress responses is still poorly understood. Read More

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http://dx.doi.org/10.1016/j.euroneuro.2019.03.001DOI Listing

Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System.

Neuron 2019 Mar 4. Epub 2019 Mar 4.

Department of Anesthesiology, Washington University Pain Center, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110, USA. Electronic address:

Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. Read More

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http://dx.doi.org/10.1016/j.neuron.2019.02.029DOI Listing

Transmission of CMV, HTLV-1, and HIV through breastmilk.

Lancet Child Adolesc Health 2019 Apr;3(4):264-273

Pathogenesis and Control of Chronic Infection, INSERM, University Montpellier, Etablissement Français du Sang, CHU de Montpellier, Montpellier, France.

Breastfeeding is a crucial child survival intervention. However, the potential for transmission of viral infections from mother to child presents the dilemma of how best to interpret the benefits and risks of breastfeeding in different settings. In this Review, we compare the transmission dynamics, risk factors, and outcomes of infection with three chronic viruses transmitted through breastmilk: cytomegalovirus, human T-cell lymphotropic virus type 1, and HIV. Read More

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http://dx.doi.org/10.1016/S2352-4642(19)30024-0DOI Listing

Tuberculosis - Depression syndemic: A public health challenge.

Indian J Tuberc 2019 Jan 26;66(1):197-202. Epub 2019 Feb 26.

Santosh University, Ghaziabad, UP, India; National Institute of Tuberculosis and Respiratory Diseases, Delhi, India; JIPMER, Pondicherry, India. Electronic address:

Introduction: Depression is common in Tuberculosis (TB) and associated with adverse outcomes through pathogenic mechanisms and impaired self-care behaviours including reduced treatment adherence. Undiagnosed depression can threaten the robustness of DOTS model despite large public health investment. The Depression-Tuberculosis Syndemic requires collaborative partnership with mental health professionals. Read More

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http://dx.doi.org/10.1016/j.ijtb.2019.02.007DOI Listing
January 2019

Patient and disease characteristics of type-2 diabetes patients with or without chronic kidney disease: an analysis of the German DPV and DIVE databases.

Cardiovasc Diabetol 2019 Mar 16;18(1):33. Epub 2019 Mar 16.

Institut für Epidemiologie und medizinische Biometrie, ZIBMT; Universität Ulm, Ulm, Germany.

Background: To evaluate the characteristics of type 2 diabetes (T2DM) patients with or without chronic kidney disease (CKD) in Germany.

Methods: Using combined DPV/DIVE registry data, the analysis included patients with T2DM at least ≥ 18 years old who had an estimated glomerular filtration rate (eGFR) value available. CKD was defined as an eGFR < 60 mL/min/1. Read More

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http://dx.doi.org/10.1186/s12933-019-0837-xDOI Listing

Polydrug use disorders in individuals with opioid use disorder.

Drug Alcohol Depend 2019 Feb 28;198:28-33. Epub 2019 Feb 28.

Addictions Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Departments of Family and Community Medicine, Pharmacology and Toxicology, and Psychiatry, Institute of Medical Sciences, University of Toronto, Toronto, Canada; Campbell Family Mental Health Research Institute, CAMH, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Background: Understanding the association of polydrug use disorders (PUD) with psychosocial and clinical factors is essential for the treatment of individuals with opioid use disorder (OUD). The aim of this study is to examine whether there is an association between childhood maltreatment, mood disorders, anxiety disorders, personality disorders, or posttraumatic stress disorder (PTSD) and PUD in individuals with OUD.

Methods: We used data from 356 individuals with OUD in the past 12 months from a nationally representative database in the United States. Read More

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http://dx.doi.org/10.1016/j.drugalcdep.2019.01.031DOI Listing
February 2019

A UHPLC-MS/MS method coupled with simple and efficient alkaline hydrolysis for free and total determination of conjugate nanomedicine: Pharmacokinetic and biodistribution study of poly (l-glutamic acid)-graft-methoxy poly (ethylene glycol)/combretastatin A4.

J Pharm Biomed Anal 2019 Mar 5;169:215-224. Epub 2019 Mar 5.

College of Pharmacy, Laboratory Animal Science and Technology Center, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, 330004, PR China. Electronic address:

Poly (l-glutamic acid)-Combretastatin A4 conjugate (PLG-CA4) is a novel nano-anticancer drug. For macromolecule conjugate nanomedicine, its pharmacology mechanism is closely related to the pharmacokinetic profiles in vivo. It is a great significance that evaluates this polymer drug combined by covalently bound via studying the pharmacokinetics and distribution characteristics. Read More

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http://dx.doi.org/10.1016/j.jpba.2019.03.001DOI Listing

Mitochondria in precision medicine; linking bioenergetics and metabolomics in platelets.

Redox Biol 2019 Mar 10;22:101165. Epub 2019 Mar 10.

Mitochondrial Medicine Laboratory, Department of Pathology, University of Alabama at Birmingham, UK. Electronic address:

Mitochondria possess reserve bioenergetic capacity, supporting protection and resilience in the face of disease. Approaches are limited to understand factors that impact mitochondrial functional reserve in humans. We applied the mitochondrial stress test (MST) to platelets from healthy subjects and found correlations between energetic parameters and mitochondrial function. Read More

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http://dx.doi.org/10.1016/j.redox.2019.101165DOI Listing

Interaction of nutrition and genetics via DNMT3L-mediated DNA methylation determines cognitive decline.

Neurobiol Aging 2019 Feb 13;78:64-73. Epub 2019 Feb 13.

School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK. Electronic address:

Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding variant within the DNA methyltransferase gene DNMT3L (R278G, A/G) by examining B vitamin intake, homocysteine levels, cognitive performance, and brain atrophy in individuals in the VITACOG study of mild cognitive impairment and the TwinsUK cohort. Read More

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http://dx.doi.org/10.1016/j.neurobiolaging.2019.02.001DOI Listing
February 2019

Is Capillary Electrophoresis a New Tool to Monitor Acute Lithium Poisoning in Human?†.

J Anal Toxicol 2019 Mar 16. Epub 2019 Mar 16.

Service de biochimie générale, Hôpital universitaire Necker-Enfants Malades, AP-HP, 149 rue de Sèvres, Paris, France.

A 38-year-old man was admitted in the intensive care unit (ICU) after supposed ingestion of 504 sustained-release tablets of Theralithe™ corresponding ~200 g of lithium carbonate. At the admission, ~19.5 h after ingestion, the patient was conscious with trembling limbs, intense thirst, profuse sweats and vomiting and lithium serum concentration was 14. Read More

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http://dx.doi.org/10.1093/jat/bkz013DOI Listing

Effect of Pterostilbene, a Natural Analog of Resveratrol, on the Activity of some Antiepileptic Drugs in the Acute Seizure Tests in Mice.

Neurotox Res 2019 Mar 15. Epub 2019 Mar 15.

Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033, Lublin, Poland.

Pterostilbene (PTE), a natural analog of resveratrol, is available both as a diet ingredient and a dietary supplement. The present study was undertaken to assess the effect of PTE on the activity of antiepileptic drugs in the acute seizure tests in mice, i.e. Read More

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http://dx.doi.org/10.1007/s12640-019-00021-1DOI Listing

Pharmacology of Nutraceuticals with Lipid Lowering Properties.

High Blood Press Cardiovasc Prev 2019 Mar 15. Epub 2019 Mar 15.

Department of Molecular Medicine, University of Padova, Padua, Italy.

Lowering total and, in particular, LDL cholesterol reduces cardiovascular risk and clinical events. Cholesterol-lowering strategies are manifold. Better diets and positive lifestyle changes are the foremost approach; the use of functional foods, of food supplements/nutraceuticals, and pharmacological treatment must be considered in patients with increasing lipid abnormalities and or increasing cardiovascular risk. Read More

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http://dx.doi.org/10.1007/s40292-019-00311-xDOI Listing

Cannabimimetic plants: are they new cannabinoidergic modulators?

Planta 2019 Mar 15. Epub 2019 Mar 15.

Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, Brescia, Italy.

Main Conclusion: Phytochemicals and secondary metabolites able to interact with the endocannabinoid system (Cannabimimetics) have been recently described in a broad range of plants and fruits. These findings can open new alternative avenues to explore for the development of novel therapeutic compounds. The cannabinoids regulate many physiological and pathological functions in both animals and plants. Read More

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http://link.springer.com/10.1007/s00425-019-03138-x
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http://dx.doi.org/10.1007/s00425-019-03138-xDOI Listing
March 2019
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Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity.

Acta Neuropathol 2019 Mar 15. Epub 2019 Mar 15.

Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Ave, E516, Cleveland, OH, 44106-4970, USA.

Both α-Synuclein (αSyn) accumulation and mitochondrial dysfunction have been implicated in the pathology of Parkinson's disease (PD). Although studies suggest that αSyn and its missense mutant, A53T, preferentially accumulate in the mitochondria, the mechanisms by which αSyn and mitochondrial proteins regulate each other to trigger mitochondrial and neuronal toxicity are poorly understood. ATP-dependent Clp protease (ClpP), a mitochondrial matrix protease, plays an important role in regulating mitochondrial protein turnover and bioenergetics activity. Read More

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http://dx.doi.org/10.1007/s00401-019-01993-2DOI Listing
March 2019
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Impact of health technology assessment and managed entry schemes on reimbursement decisions of centrally authorised medicinal products in Belgium.

Eur J Clin Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

Department of clinical pharmacology and pharmacotherapy, Vrije Universiteit Brussel, Brussels, Belgium.

Purpose: Centrally authorised medicinal products (CAMPs) in the European Union may offer added therapeutic value (ATV) but may be linked to high prices and limited efficiency. Health technology assessment (HTA) and managed entry schemes (MES) may facilitate the reimbursement decision by providing reliable estimates of the medicinal product's value and costs and by controlling the remaining uncertainty, respectively. We investigated the impact of HTA criteria and the initiation of a MES on the reimbursement decision of CAMPs in Belgium. Read More

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http://dx.doi.org/10.1007/s00228-019-02665-6DOI Listing

The effect of neutropenia on the clinical pharmacokinetics of vancomycin in adults.

Eur J Clin Pharmacol 2019 Mar 15. Epub 2019 Mar 15.

Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.

Aim: There is accumulating evidence that neutropenic patients require higher dosages of vancomycin. To prevent sub-therapeutic drug exposure, it is of utmost importance to obtain adequate exposure from the first dose onwards. We aimed to quantify the effect of neutropenia on the pharmacokinetics of vancomycin. Read More

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http://dx.doi.org/10.1007/s00228-019-02657-6DOI Listing

Insulin-stimulated mTOR activation in peripheral blood mononuclear cells associated with early treatment response to lithium augmentation in rodent model of antidepressant-resistance.

Transl Psychiatry 2019 Mar 15;9(1):113. Epub 2019 Mar 15.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.

Lithium has been shown to have some therapeutic efficacy as an adjunctive treatment for intractable forms of major depression. Activation of mammalian target of rapamycin (mTOR) and inhibition of glycogen synthase kinase-3β (GSK3β) have been implicated in its putative mechanisms of action. These proteins are integral components of the insulin signaling pathway, which may serve as a critical co-regulator of drug action. Read More

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http://dx.doi.org/10.1038/s41398-019-0434-5DOI Listing

Networks of electrostatic and hydrophobic interactions modulate the complex folding free energy surface of a designed βα protein.

Proc Natl Acad Sci U S A 2019 Mar 15. Epub 2019 Mar 15.

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605;

The successful de novo design of proteins can provide insights into the physical chemical basis of stability, the role of evolution in constraining amino acid sequences, and the production of customizable platforms for engineering applications. Previous guanidine hydrochloride (GdnHCl; an ionic denaturant) experiments of a designed, naturally occurring βα fold, Di-III_14, revealed a cooperative, two-state unfolding transition and a modest stability. Continuous-flow mixing experiments in our laboratory revealed a simple two-state reaction in the microsecond to millisecond time range and consistent with the thermodynamic results. Read More

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http://dx.doi.org/10.1073/pnas.1818744116DOI Listing

The emerging role of sorting nexins in cardiovascular diseases.

Clin Sci (Lond) 2019 Mar 15;133(5):723-737. Epub 2019 Mar 15.

Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing 400042, P.R. China

The sorting nexin (SNX) family consists of a diverse group of cytoplasmic- and membrane-associated phosphoinositide-binding proteins that play pivotal roles in the regulation of protein trafficking. This includes the entire endocytic pathway, such as endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNX pathway are involved in several forms of cardiovascular disease (CVD). Read More

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http://dx.doi.org/10.1042/CS20190034DOI Listing

SWI/SNF-compromised cancers are susceptible to bromodomain inhibitors.

Cancer Res 2019 Mar 15. Epub 2019 Mar 15.

Experimental Medecine, Lady Davis Institut

The antitumor activity of bromodomain and extra-terminal motif protein inhibitors (BETi) has been demonstrated across numerous types of cancer. As such, these inhibitors are currently undergoing widespread clinical evaluation. However, predictive biomarkers allowing the stratification of tumors into responders and non-responders to BETi are lacking. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1545DOI Listing

Intratumoral genetic and functional heterogeneity in pediatric glioblastoma.

Cancer Res 2019 Mar 15. Epub 2019 Mar 15.

Physiology & Pharmacology, Biochemistry & Molecular Biology, University of Calgary

Pediatric glioblastoma (pGBM) is a lethal cancer with no effective therapies. To understand the mechanisms of tumor evolution in this cancer, we performed whole genome sequencing with linked reads on longitudinally resected pGBM samples. Our analyses showed that all diagnostic and recurrent samples were collections of genetically diverse subclones. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3441DOI Listing

Protein translocation by the SecA ATPase occurs by a power-stroke mechanism.

EMBO J 2019 Mar 15. Epub 2019 Mar 15.

Department of Cell Biology, Harvard Medical School, Boston, MA, USA

SecA belongs to the large class of ATPases that use the energy of ATP hydrolysis to perform mechanical work resulting in protein translocation across membranes, protein degradation, and unfolding. SecA translocates polypeptides through the SecY membrane channel during protein secretion in bacteria, but how it achieves directed peptide movement is unclear. Here, we use single-molecule FRET to derive a model that couples ATP hydrolysis-dependent conformational changes of SecA with protein translocation. Read More

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http://dx.doi.org/10.15252/embj.2018101140DOI Listing

The role and therapeutic potential of connexins, pannexins and their channels in Parkinson's disease.

Cell Signal 2019 Mar 12. Epub 2019 Mar 12.

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address:

Lack of effective medication for slowing down progression of Parkinson's disease (PD) as a highly prevalent neurodegenerative disorder requires novel avenues of scientific investigation to elucidate the underlying molecular and cellular mechanisms. Studying connexins, pannexins and their channels has uncovered their potential role in mediating communication and signaling pathways that drive neurodegenerative diseases, including PD. Indeed, given their critical role in tissue homeostasis, it is not surprising that connexins, pannexins and their channels are frequently involved in pathological processes. Read More

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http://dx.doi.org/10.1016/j.cellsig.2019.03.010DOI Listing
March 2019
4.315 Impact Factor
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