6,073,369 results match your criteria Pharmacology & Therapeutics[Journal]

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Turning Pain into Gain: Evaluation of a Multidisciplinary Chronic Pain Management Program in Primary Care.

Pain Med 2018 Dec 12. Epub 2018 Dec 12.

School of Pharmacy and Pharmacology, Gold Coast Campus, Griffith University, Queensland 4222, Australia and Menzies Health Institute Queensland, Gold Coast Campus, Griffith University, Queensland 4222, Australia.

Objective: To measure the impact of the multidisciplinary Turning Pain Into Gain program in people experiencing chronic pain of any etiology.

Methods: A mixed-methods observational study of 252 participants was used to explore the impact of Turning Pain Into Gain on medication use; quality of life and functioning, as measured by the Pain Self-Efficacy Questionnaire; and self-reported hospitalizations between 2015 and 2016.

Results: Responses from 178 participants showed an increased alignment with Australian pain medication guidelines (e. Read More

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December 2018

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking.

Stem Cell Reports 2018 Dec;11(6):1365-1377

Global Safety Pharmacology, Non-Clinical Safety, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Read More

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December 2018

IP Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca to Lysosomes.

Cell Rep 2018 Dec;25(11):3180-3193.e7

Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. Electronic address:

Inositol 1,4,5-trisphosphate (IP) receptors (IPRs) allow extracellular stimuli to redistribute Ca from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H-ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca released by all IPR subtypes, but not Ca entering cells through store-operated Ca entry (SOCE). A low-affinity Ca sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca] during IP-evoked Ca release, but not during SOCE. Read More

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December 2018

Dopamine Cells Differentially Regulate Striatal Cholinergic Transmission across Regions through Corelease of Dopamine and Glutamate.

Cell Rep 2018 Dec;25(11):3148-3157.e3

Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address:

The balance of dopamine and acetylcholine in the dorsal striatum is critical for motor and learning functions. Midbrain dopamine cells and local cholinergic interneurons (ChIs) densely innervate the striatum and have strong reciprocal actions on each other. Although dopamine inputs regulate ChIs, the functional consequences of dopamine neuron activity across dorsal striatal regions is poorly understood. Read More

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December 2018

PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer.

Cell Rep 2018 Dec;25(11):2972-2980.e5

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

PARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in mice bearing Brca1-deficient ovarian tumors. Read More

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December 2018

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target.

ACS Chem Neurosci 2018 Dec 12. Epub 2018 Dec 12.

While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials and GPR88 endogenous ligands remain unknown. Read More

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December 2018

Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study.

PLoS One 2018 12;13(12):e0208796. Epub 2018 Dec 12.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.

Background: The number of patients with diabetes is increasing particularly in Asia-Pacific region. Many of them are treated with antidiabetics. As the basis of the studies on the benefit and harm of antidiabetic drugs in the region, the information on patterns of market penetration of new classes of antidiabetic medications is important in providing context for subsequent research and analyzing and interpreting results. Read More

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December 2018

Correlation and prognostic accuracy between noninvasive liver fibrosismarkers and portal pressure in cirrhosis: Role of ALBI score.

PLoS One 2018 12;13(12):e0208903. Epub 2018 Dec 12.

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The role of noninvasive liver fibrosis markers which were developed to evaluate the severity of chronic liver disease remains unclear in cirrhosis.

Aims: To evaluate the correlation between noninvasive markers and hemodynamic parameters and their prognostic performance in cirrhotic patients.

Methods: A total of 242 cirrhotic patients undergoing hemodynamic study were analyzed. Read More

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December 2018

Effects of intravenous AICAR (5-aminoimidazole-4-carboximide riboside) administration on insulin signaling and resistance in premature baboons, Papio sp.

PLoS One 2018 12;13(12):e0208757. Epub 2018 Dec 12.

Department of Medicine, Division of Diabetes, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.

Premature baboons exhibit peripheral insulin resistance and impaired insulin signaling. 5' AMP-activated protein kinase (AMPK) activation improves insulin sensitivity by enhancing glucose uptake (via increased glucose transporter type 4 [GLUT4] translocation and activation of the extracellular signal-regulated kinase [ERK]/ atypical protein kinase C [aPKC] pathway), and increasing fatty acid oxidation (via inhibition of acetyl-CoA carboxylase 1 [ACC]), while downregulating gluconeogenesis (via induction of small heterodimer partner [SHP] and subsequent downregulation of the gluconeogenic enzymes: phosphoenolpyruvate carboxykinase [PEPCK], glucose 6-phosphatase [G6PASE], fructose- 1,6-bisphosphatase 1 [FBP1], and forkhead box protein 1 [FOXO1]). The purpose of this study was to investigate whether pharmacologic activation of AMPK with AICAR (5-aminoimidazole-4-carboximide riboside) administration improves peripheral insulin sensitivity in preterm baboons. Read More

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December 2018

Increased Alzheimer's risk during the menopause transition: A 3-year longitudinal brain imaging study.

PLoS One 2018 12;13(12):e0207885. Epub 2018 Dec 12.

Departments of Pharmacology and Neurology, College of Medicine, University of Arizona, Tucson, United States of America.

Two thirds of all persons with late-onset Alzheimer's disease (AD) are women. Identification of sex-based molecular mechanisms underpinning the female-based prevalence of AD would advance development of therapeutic targets during the prodromal AD phase when prevention or delay in progression is most likely to be effective. This 3-year brain imaging study examines the impact of the menopausal transition on Alzheimer's disease (AD) biomarker changes [brain β-amyloid load via 11C-PiB PET, and neurodegeneration via 18F-FDG PET and structural MRI] and cognitive performance in midlife. Read More

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December 2018

Antiemetic Drug Use in Children: What the Clinician Needs to Know.

J Pediatr Gastroenterol Nutr 2018 Dec 11. Epub 2018 Dec 11.

Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Parma, Italy.

Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as "off-label", outside their authorized drug label. Read More

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December 2018

A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients.

Nurs Res 2019 Jan/Feb;68(1):73-79

Mary Fran Tracy, PhD, RN, APRN, CNS, FAAN, is Associate Professor, University of Minnesota School of Nursing, and Nurse Scientist, University of Minnesota Medical Center, Minneapolis. Linda Chlan, PhD, RN, ATSF, FAAN, is Associate Dean for Nursing Research and Professor of Nursing, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. Kay Savik, MS, is Senior Statistician, University of Minnesota School of Nursing, Minneapolis. Debra J. Skaar, PharmD, FCCM, is Associate Professor of Experimental & Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis. Craig Weinert, MD, MPH, is Professor of Medicine, Pulmonary, Allergy, Critical Care, and Sleep Medicine Division, University of Minnesota Medical School, Minneapolis.

Background: Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge.

Objectives: The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies.

Methods: Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Read More

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December 2018

Population pharmacokinetic analysis of bisoprolol in patients with acute coronary syndrome.

J Cardiovasc Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Serbia.

To date, many questions about the extent and cause of pharmacokinetic variability of even the most widely studied and prescribed β1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was carried out using a non-linear mixed effects model (NONMEM), version 7. Read More

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December 2018

Voluntary wheel running reveals sex specific nociceptive factors in murine experimental autoimmune encephalomyelitis.

Pain 2018 Dec 11. Epub 2018 Dec 11.

Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada, T6G 2E1.

Multiple Sclerosis (MS) is an inflammatory, neurodegenerative autoimmune disease associated with sensory and motor dysfunction. Although estimates vary, ∼50% of patients with MS experience pain during their disease. The mechanisms underlying the development of pain are not fully understood and no effective treatment for MS related pain is available. Read More

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December 2018

Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths.

JAMA Psychiatry 2018 Dec 12. Epub 2018 Dec 12.

Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.

Importance: Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.

Objective: To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.

Design, Setting, And Participants: This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Read More

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December 2018
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Housefly (Musca domestica) larvae powder, preventing oxidative stress injury via regulation of UCP4 and CyclinD1 and modulation of JNK and P38 signaling in APP/PS1 mice.

Food Funct 2018 Dec 12. Epub 2018 Dec 12.

School of Basic Courses, Guangzhou, Guangdong 510006, China and Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangzhou, Guangdong 510006, China and Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong 510006, China.

Housefly (Musca domestica) Larvae powder (HL) is rich in antioxidants. As oxidative stress is considered as one of the main pathogenesis in Alzheimer's Disease (AD), this study was designed to explore the protective effects of HL as an antioxidant on APP/PS1 mice. 2-Month-old APP/PS1 mice were divided into a model control (MC) group, a Donepezil group and a HL group, and C57BL/6 mice were used as the normal control (NC) group. Read More

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December 2018

Cardiac Vagus and Exercise.

Physiology (Bethesda) 2019 Jan;34(1):71-80

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London , London , United Kingdom.

Lower resting heart rate and high autonomic vagal activity are strongly associated with superior exercise capacity, maintenance of which is essential for general well-being and healthy aging. Recent evidence obtained in experimental studies using the latest advances in molecular neuroscience, combined with human exercise physiology, physiological modeling, and genomic data suggest that the strength of cardiac vagal activity causally determines our ability to exercise. Read More

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January 2019

Development of a risk-based, large-group revision quiz for first-year undergraduates.

Adv Physiol Educ 2019 Mar;43(1):42-46

School of Physiology, Pharmacology and Neuroscience, University of Bristol , Bristol , United Kingdom.

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Clinical Features of Primary Familial Brain Calcification in 17 Families.

Chin Med J (Engl) 2018 Dec;131(24):2997-3000

Department of Clinical Pharmacology, Xiangya Hospital Central South University, Changsha, Hunan 410008, China.

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December 2018

Radioprotective effect of melatonin on expression of and genes in rat peripheral blood.

J Cancer Res Ther 2018 Dec;14(Supplement):S1070-S1075

Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Ionizing radiation is a critical threat to biomolecules, especially DNA. Various combinatorial compounds have been studied to protect this biomolecule. Melatonin has been reported as a direct and indirect free radical scavenger, but in this study, we explored the effect of melatonin on assisting in DNA repair by expression of Cdkn1a and Rad50; both of these genes are involved in DNA repair signaling, induced by radiation in rat peripheral blood. Read More

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December 2018

Basics on the use of acid-sensing ion channels' inhibitors as therapeutics.

Neural Regen Res 2019 Mar;14(3):395-398

North Texas Eye Research Institute, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.

Since the discovery of acid-sensing ion channels in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. Acid-sensing ion channels play important roles in mediating pain sensation during diseases such as stroke, inflammation, arthritis, cancer, and recently migraine. More interestingly, acid-sensing ion channels may explain the sex differences in pain between males and females. Read More

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Neuroinflammation as a target for glaucoma therapy.

Neural Regen Res 2019 Mar;14(3):391-394

Visual Neurophysiology and Neurophthalmology Research Unit, IRCCS G.B. Bietti Foundation, Roma, Italy.

The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation - involving the activation and proliferation of resident glial cells (astrocytes, Muller cells and microglia) and the release of a plethora of anti- and pro-inflammatory cytokines, chemokines and reactive oxygen species - has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. Read More

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Moving from the present to the future of Postural Tachycardia Syndrome - What we need.

Auton Neurosci 2018 Dec 4;215:126-128. Epub 2018 Jul 4.

Autonomic Dysfunction Center, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.

Our understanding about Postural Tachycardia Syndrome (POTS) has advanced significantly over the last 25 years. Despite the significant advances that have been made in defining the syndrome and finding some treatments for our patients, there is much work to be done to significantly improve our understanding of the disorder and improve therapeutics. In this article, 5 NEEDS are identified that will be required over the next several years if we want future care to move beyond where we are in the present. Read More

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December 2018

Terpenoid-rich Elettaria cardamomum extract prevents Alzheimer-like alterations induced in diabetic rats via inhibition of GSK3β activity, oxidative stress and pro-inflammatory cytokines.

Cytokine 2019 Jan 24;113:405-416. Epub 2018 Oct 24.

Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Purpose: Recent studies suggested that the non-familiar form of Alzheimer's disease (AD) could be consequence of metabolic syndrome and neuroinflammation. Elettaria cardamomum extract (EC) has exhibited antidiabetic, antioxidant and anti-inflammatory properties. This research was conducted to evaluate the effects of EC on AD-like alterations in rats induced by high fructose and high fat diet coupled with a single small dose of STZ (25 mg/kg) (T2DM rats). Read More

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January 2019

Peripheral oxytocin and vasopressin modulates regional brain activity differently in men and women with schizophrenia.

Schizophr Res 2018 Dec 6;202:173-179. Epub 2018 Jul 6.

Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States of America; Department of Psychiatry, University of Cincinnati, United States of America.

Background: Oxytocin (OT) and arginine vasopressin (AVP) exert sexually dimorphic effects on cognition and emotion processing. Abnormalities in these hormones are observed in schizophrenia and may contribute to multiple established sex differences associated with the disorder. Here we examined sex-dependent hormone associations with resting brain activity and their clinical associations in schizophrenia patients. Read More

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December 2018

Potential Applications of Induced Pluripotent Stem Cells for Cardiovascular Diseases.

Curr Drug Targets 2018 Dec 11. Epub 2018 Dec 11.

Department of Clinical Pharmacy, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China; and Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081. China.

Cardiovascular disease (CVD) is the number one killer of human beings which has long become the disease with the highest incidence and disability rate in modern society. Currently induced pluripotent stem cells (iPSCs), with the potential to form fresh myocardium and better safety than other stem cells, are widely used in the CVD therapy studies. Moreover, iPSC-derived cardiomyocytes (CMs), as a novel disease model, appear to play an important role in new drug screening, drug safety assessment, and pathological mechanisms of disease. Read More

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December 2018

The impact of obesity as an independent risk factor for the development of renal injury: implications from rat models of obesity.

Am J Physiol Renal Physiol 2018 Dec 12. Epub 2018 Dec 12.

Pharmacology and Toxicology, University of Mississippi Medical Center, United States.

Diabetes and hypertension are the major causes of chronic kidney disease (CKD). Epidemiological studies within the last few decades have revealed that obesity-associated renal disease is a emerging epidemic and that the increasing prevalence of obesity parallels the increased rate of CKD. This has led to the inclusion of obesity as an independent risk factor for CKD. Read More

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December 2018

Down-Regulation of APTR and it's Diagnostic Value in Papillary and Anaplastic Thyroid Cancer.

Pathol Oncol Res 2018 Dec 11. Epub 2018 Dec 11.

Department of General Surgery, Department of Hepatopancreatobiliary Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Tongbai Road #195, Zhengzhou, 450007, Henan, China.

APTR has been employed as a potential biomarker attributing to it was involved in carcinogenesis and malignancy's progression. However, the roles of APTR in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) are unclear. In the present study, we aimed to explore the relative expression of APTR in PTC and ATC tissues and the relation between APTR expression and PTC clinicopathological features. Read More

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December 2018

Monoclonal Antibodies for the Treatment of Melanoma: Present and Future Strategies.

Methods Mol Biol 2019 ;1904:83-108

Department of Clinical Pharmacology, Genentech Research and Early Development, South San Francisco, CA, USA.

Metastatic melanoma is a dreadful type of skin cancer arising due to uncontrolled proliferation of melanocytes. It has very poor prognosis, low 5-year survival rates and until recently there were only handful of treatment options for metastatic melanoma patients. The drugs that were approved for the treatment had low response rates and were associated with severe adverse events. Read More

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January 2019
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Processing of Primary Patient Tumors and Subsequent Generation of Primary Cell Lines.

Methods Mol Biol 2019 ;1897:425-431

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Patient tumor tissue processing is an important step in the generation of clinically relevant specimens for in vitro and in vivo studies. Proper disassociation and tissue sample cleanup is a multistep, time-consuming process that ultimately effects the generation of patient derived xenografts and neurosphere cultures. Here we describe a detailed protocol on how to process and disassociate patient glioma tissue and subsequent steps on orthotopic implantation and in vitro generation of neurospheres. Read More

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January 2019

Biosafety and Biohazards: Understanding Biosafety Levels and Meeting Safety Requirements of a Biobank.

Methods Mol Biol 2019 ;1897:213-225

Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

When it comes to biobanking and working with different types of laboratory specimens, it is important to understand potential biohazards to ensure safety of the operator and laboratory personnel. Biological safety levels (BSL) are a series of designations used to inform laboratory personnel about the level of biohazardous risks in a laboratory setting. There are a total of four levels ranked in order of increasing risk as stipulated by the Center of Disease Control and Prevention (CDC) (Biosafety in microbiological and biomedical laboratories, 5th edn. Read More

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January 2019

ATP Synthase Subunit Beta Immunostaining is Reduced in the Sclerotic Hippocampus of Epilepsy Patients.

Cell Mol Neurobiol 2018 Dec 11. Epub 2018 Dec 11.

Department of Anatomical Pathology, School of Medical Sciences, University of Campinas (UNICAMP), Av. Tessália Vieira de Camargo, 126, Campinas, SP, CEP 13083-887, Brazil.

Epilepsy is a common disease presenting with recurrent seizures. Hippocampal sclerosis (HS) is the commonest histopathological alteration in patients with temporal lobe epilepsy (TLE) undergoing surgery. HS physiopathogenesis is debatable. Read More

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December 2018

The potential protective effect of two actinomycete extracts against carbon tetrachloride-induced hepatotoxicity in rats.

Environ Sci Pollut Res Int 2018 Dec 11. Epub 2018 Dec 11.

Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.

The aim of this study was to investigate the potential protective effect of two extracts derived from two soil actinomycete strains, designated S19 and G30, against CCl4-induced hepatotoxicity in male rats. Sixty-four male rats were divided into four groups of 16 rats per group. The first group was a control group given corn oil and the nutritive medium which is composed of a mixture of the two used media. Read More

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December 2018

Activation of somatodendritic 5-HT autoreceptors reduces the acquisition and expression of cued fear in the rat fear-potentiated startle test.

Psychopharmacology (Berl) 2018 Dec 12. Epub 2018 Dec 12.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.

Rationale: Fear conditioning is an important factor in the etiology of anxiety disorders. Previous studies have demonstrated a role for serotonin (5-HT) receptors in fear conditioning. However, the relative contribution of somatodendritic 5-HT autoreceptors and post-synaptic 5-HT heteroreceptors in fear conditioning is still unclear. Read More

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December 2018

International Space Station conditions alter genomics, proteomics, and metabolomics in Aspergillus nidulans.

Appl Microbiol Biotechnol 2018 Dec 12. Epub 2018 Dec 12.

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Rm 406A, Los Angeles, CA, 90089-9121, USA.

The first global genomic, proteomic, and secondary metabolomic characterization of the filamentous fungus Aspergillus nidulans following growth onboard the International Space Station (ISS) is reported. The investigation included the A. nidulans wild-type and three mutant strains, two of which were genetically engineered to enhance secondary metabolite production. Read More

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December 2018

Evaluation of the effects of an oral notch inhibitor, crenigacestat (LY3039478), on QT interval, and bioavailability studies conducted in healthy subjects.

Cancer Chemother Pharmacol 2018 Dec 11. Epub 2018 Dec 11.

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.

Purpose: Crenigacestat (LY3039478) is a Notch inhibitor currently being investigated in advanced cancer patients. Conducting clinical pharmacology studies in healthy subjects avoids nonbeneficial drug exposures in cancer patients and mitigates confounding effects of disease state and concomitant medications.

Methods: Three studies were conducted in healthy subjects, assessing safety, pharmacokinetics, effect on QT interval, and relative and absolute bioavailability of crenigacestat. Read More

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December 2018

Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: its implication in cancer therapeutics.

Cell Mol Life Sci 2018 Dec 11. Epub 2018 Dec 11.

Department of Life Science, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India.

The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Read More

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December 2018
5.808 Impact Factor

The FAK inhibitor BI 853520 inhibits spheroid formation and orthotopic tumor growth in malignant pleural mesothelioma.

J Mol Med (Berl) 2018 Dec 11. Epub 2018 Dec 11.

Division of Thoracic Surgery, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.

No tyrosine kinase inhibitors are approved for malignant pleural mesothelioma (MPM). Preclinical studies identified focal adhesion kinase (FAK) as a target in MPM. Accordingly, we assessed the novel, highly selective FAK inhibitor (BI 853520) in 2D and 3D cultures and in vivo. Read More

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December 2018

An update on sargramostim for treatment of acute radiation syndrome.

Authors:
V K Singh T M Seed

Drugs Today (Barc) 2018 Nov;54(11):679-693

Tech Micro Services, Bethesda, Maryland, USA.

The potential use by terrorists of an improvised nuclear device, a radiological dispersal device, or an unintended nuclear/radiological accident in heavily populated areas is a national security threat of major consequences. Although this type of security threat is considered to be low-risk, it would have a devastating impact. Health issues would be a major concern; medical care would be necessary for all those who received considerable radiation exposure (> 1 Gy) leading to hematopoietic acute radiation syndrome (ARS). Read More

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November 2018
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Estradiol vaginal inserts (Imvexxy): effective in genitourinary syndrome of menopause without increasing systemic estrogen levels.

Authors:
D M Paton

Drugs Today (Barc) 2018 Nov;54(11):667-677

Professor Emeritus of Pharmacology, University of Auckland, Auckland, New Zealand.

Many women suffer from the genitourinary syndrome of the menopause (GSM), in particular pathological changes that occur in the vagina due to the reduction in their production of estrogens. TherapeuticsMD has developed Imvexxy, small softgel capsules that contain solubilized estradiol and that are inserted vaginally by women twice a week, every 3 to 4 days. These vaginal inserts have been found to readily supply estradiol to the vagina and to result in significant improvement in the GSM signs and symptoms these women had been experiencing. Read More

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November 2018

Avatrombopag maleate for the treatment of periprocedural thrombocytopenia in patients with chronic liver disease.

Authors:
H Al-Samkari

Drugs Today (Barc) 2018 Nov;54(11):647-655

Division of Hematology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Avatrombopag maleate (Doptelet; Dova Pharmaceuticals) is an oral, small-molecule second-generation thrombopoietin (TPO) receptor agonist under development for the treatment of thrombocytopenia. Recently approved by the U.S. Read More

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November 2018

Oxidation-Reduction Potential in Patients undergoing Transcatheter or Surgical Aortic Valve Replacement.

Biomed Res Int 2018 14;2018:8469383. Epub 2018 Nov 14.

Department of Anesthesiology, Medical Faculty, RWTH Aachen University, Aachen, Germany.

Background: Aortic valve stenosis has gained increasingly more importance due to its high prevalence in elderly people. More than two decades ago, transcatheter aortic valve replacement emerged for patients who were denied surgery, and its noninferiority has been demonstrated in numerous studies. Oxidative stress has generated great interest because of its sensitivity to cell damage and the possibility of offering early hints of clinical outcomes. Read More

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November 2018

Are There Limitations to Exercise Benefits in Peripheral Arterial Disease?

Front Cardiovasc Med 2018 27;5:173. Epub 2018 Nov 27.

Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States.

Substantial evidence exists indicating that inactivity contributes to the progression of chronic disease, and conversely, that regular physical activity can both prevent the onset of disease as well as delay the progression of existing disease. To that end "exercise as medicine" has been advocated in the broad context as general medical care, but also in the specific context as a therapeutic, to be considered in much the same way as other drugs. As there are non-responders to many medications, there also are non-responders to exercise; individual who participate but do not demonstrate appreciable improvement/benefit. Read More

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November 2018

Homozygosity for the SCN10A Polymorphism rs6795970 Is Associated With Hypoalgesic Inflammatory Bowel Disease Phenotype.

Front Med (Lausanne) 2018 27;5:324. Epub 2018 Nov 27.

Division of Gastroenterology & Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, United States.

Hypoalgesic inflammatory bowel disease (IBD), a condition in which patients with active disease do not perceive and/or report abdominal pain, is associated with serious complications and there is a lack of cost-effective, reliable diagnostic methods to identify "at-risk" patients. The voltage-gated sodium channels (VGSC's), Na1.7, Na1. Read More

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November 2018

Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.

Front Chem 2018 27;6:532. Epub 2018 Nov 27.

Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.

In this paper using quantum-mechanical (QM) calculations in combination with Bader's quantum theory of "Atoms in Molecules" (QTAIM) in the continuum with ε = 1, we have theoretically demonstrated for the first time that revealed recently highly-energetic conformers of the classical A·T DNA base pairs - Watson-Crick [A·T(w)], reverse Watson-Crick [A·T(w)], Hoogsteen [A·T(w)] and reverse Hoogsteen [A·T(w)] - act as intermediates of the intrapair mutagenic tautomerization of the T nucleobase owing to the novel tautomerisation pathways: A·T(w)↔A·T(w); A·T(w)↔A· (w); A·T(w)↔A·T(w); A·T(w)↔A· (w). All of them occur the transition states as tight ion pairs (A, protonated by the N6H amino group)·(T, deprotonated by the N3H group) with quasi-orthogonal geometry, which are stabilized by the participation of the strong (A)N6H···O4/O2(T) and (A)N6H···N3(T) H-bonds. Established tautomerizations proceed through a two-step mechanism of the protons moving in the opposite directions along the intermolecular H-bonds. Read More

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November 2018

Concentration and motility of spermatozoa and testosterone level of kacang goat after seminal vesicle extract administration.

Open Vet J 2018 30;8(4):406-410. Epub 2018 Oct 30.

Reproduction Laboratory, Faculty of Veterinary Medicine, Syiah Kuala University, Banda Aceh, Indonesia.

This study aimed to determine the effect of seminal vesicle extract administration to increase the concentration and motility of spermatozoa and testosterone level of kacang goat. The experiment was arranged using a randomly completely block design (RCBD). Three kacang goats were used and each goat received three treatments namely P0 (2 mL of 0. Read More

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October 2018

3-Adrenoreceptors Control Mitochondrial Dormancy in Melanoma and Embryonic Stem Cells.

Oxid Med Cell Longev 2018 13;2018:6816508. Epub 2018 Nov 13.

Neonatal Intensive Care Unit, Medical Surgical Fetal-Neonatal Department, A. Meyer Children's University Hospital, Florence, Italy.

The early phases of embryonic development and cancer share similar strategies to improve their survival in an inhospitable environment: both proliferate in a hypoxic and catecholamine-rich context, increasing aerobic glycolysis. Recent studies show that 3-adrenergic receptor (3-AR) is involved in tumor progression, playing an important role in metastasis. Among -adrenergic receptors, 3-AR is the last identified member of this family, and it is involved in cancer cell survival and induction of stromal reactivity in the tumor microenvironment. Read More

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November 2018
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Plant natural modulators in breast cancer prevention: status quo and future perspectives reinforced by predictive, preventive, and personalized medical approach.

EPMA J 2018 Dec 12;9(4):403-419. Epub 2018 Nov 12.

1Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.

In contrast to the genetic component in mammary carcinogenesis, epigenetic alterations are particularly important for the development of sporadic breast cancer (BC) comprising over 90% of all BC cases worldwide. Most of the DNA methylation processes are physiological and essential for human cellular and tissue homeostasis, playing an important role in a number of key mechanisms. However, if dysregulated, DNA methylation contributes to pathological processes such as cancer development and progression. Read More

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December 2018

Moroccan Propolis: A Natural Antioxidant, Antibacterial, and Antibiofilm against with No Induction of Resistance after Continuous Exposure.

Evid Based Complement Alternat Med 2018 12;2018:9759240. Epub 2018 Nov 12.

Department of Chemistry and Pharmacy, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, MeditBio, 8005-139 Faro, Portugal.

This study was performed to evaluate the total phenols, flavonoids, and antioxidant activities of twenty-four propolis samples from different regions of Morocco. In addition, two samples were screened regarding the antibacterial effect against four strains. Gas chromatography coupled to mass spectra (GC-MS) analysis was done for propolis samples used in antibacterial tests. Read More

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November 2018
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