6,156,907 results match your criteria Pharmacology & Therapeutics[Journal]

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Does the 5-Aminosalicylate Concentration Correlate with the Efficacy of Oral 5-Aminosalicylate and Predict Response in Patients with Inflammatory Bowel Disease? A Systematic Review.

Digestion 2019 Apr 23:1-17. Epub 2019 Apr 23.

Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Background: Oral 5-aminosalicylic acid (5-ASA, mesalazine) is the first choice therapeutic agent for treating mild-to-moderate ulcerative colitis (UC). Unfortunately a significant group of patients fail to respond. Therapeutic drug monitoring might help to maintain or induce remission by providing a tool for optimization of 5-ASA therapy. Read More

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https://www.karger.com/Article/FullText/499331
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http://dx.doi.org/10.1159/000499331DOI Listing
April 2019
1 Read

Can Digital Health Enable Higher Quality Real-World Evidence-Based Decisions?

Clin Pharmacol Ther 2019 Apr 23. Epub 2019 Apr 23.

Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Merck, Kenilworth, New Jersey, USA.

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cpt.1440
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http://dx.doi.org/10.1002/cpt.1440DOI Listing
April 2019
1 Read

Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.

J Med Chem 2019 Apr 23. Epub 2019 Apr 23.

Albany Molecular Research, Inc. , 21 Corporate Circle , Albany , New York 12203 , United States.

Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compounds was based on iterative analysis of X-ray crystal structures combined with metabolite identification. Selectivity for the activated, dimeric form of PDE4D provided potent memory enhancing effects in a mouse model of novel object recognition with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors that lack subtype selectivity. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.9b00193DOI Listing

Methodological Characteristics of Clinical Trials: Impact of Mandatory Trial Registration.

J Pharm Pharm Sci 2019 ;22(1):131-141

Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored.

Methods: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Read More

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http://dx.doi.org/10.18433/jpps30360DOI Listing
January 2019

Safety, Pharmacokinetics, and Pharmacodynamics of the Autotaxin Inhibitor GLPG1690 in Healthy Subjects: Phase 1 Randomized Trials.

J Clin Pharmacol 2019 Apr 23. Epub 2019 Apr 23.

Galapagos Biotech Limited, Cambridge, United Kingdom.

GLPG1690 is a novel autotaxin inhibitor in development for the treatment of idiopathic pulmonary fibrosis (IPF). We report phase 1 studies investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG1690 in healthy subjects. We performed a first-in-human randomized, double-blind, placebo-controlled trial of single (20, 60, 150, 300, 600, 1000, 1500 mg) and multiple (14 days: 150 mg twice daily; 600 and 1000 mg once daily) ascending oral doses of GLPG1690 (NCT02179502), and a randomized, open-label, crossover relative bioavailability study to compare the PK of tablet and capsule formulations of GLPG1690 600 mg and to assess the effect of food on PK of the tablet formulation (NCT03143712). Read More

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http://dx.doi.org/10.1002/jcph.1424DOI Listing

A phase 1 trial of the oral DNA methyltransferase inhibitor CC-486 and the histone deacetylase inhibitor romidepsin in advanced solid tumors.

Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland.

Background: Epigenetic abnormalities are manifold in all solid tumors and include changes in chromatin configuration and DNA methylation. The authors designed a phase 1 study to evaluate the oral DNA methyltransferase inhibitor CC-486 combined with the histone deacetylase inhibitor romidepsin in advanced solid tumors with dose expansion to further evaluate pharmacodynamics and possible clinical benefit of the recommended phase 2 dose (RP2D).

Methods: This was a phase 1 study with a 3 + 3 dose-escalation design and an expansion phase for patients with virally mediated cancers. Read More

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http://dx.doi.org/10.1002/cncr.32138DOI Listing

Phenolic C-Glycosides and Aglycones from Marine-Derived Aspergillus sp. and Their Anti-Inflammatory Activities.

J Nat Prod 2019 Apr 23. Epub 2019 Apr 23.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation and Department of Pharmacology, School of Pharmacy, Tongji Medical College , Huazhong University of Science and Technology , Wuhan 430030 , People's Republic of China.

A chemical investigation of the secondary metabolites of a marine-derived Aspergillus sp. led to the isolation and characterization of 13 phenolic compounds, including 10 new compounds (1-10). Seven new compounds (1-7) are unusual phenolic C-glycosides, while the other new compounds (8-10) are structurally related aglycones. Read More

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http://dx.doi.org/10.1021/acs.jnatprod.8b00744DOI Listing

[Metabolism processes and mechanisms of regulation of platelet activity (review of literature).]

Klin Lab Diagn 2019 ;64(3):164-169

Samara State Medical University, 443099, Samara, Russia.

Platelets play fundamental role in ensuring the hemostatic function in blood. In addition to this canonical function, the blood plates play angiotrophic, immunological, transport role, participate in the activation of plasma hemostasis, retraction of a blood clot, and can record circulating immune complexes. The review article presents current data on the structure and conjugation of molecular rearrangements of platelet ultrastructures associated with the functioning of an open canalicular platelet system, a dense tubular system, and a platelet cytoplasmic membrane. Read More

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http://dx.doi.org/10.18821/0869-2084-2019-64-3-164-169DOI Listing
January 2019

Evidence of a Clinically Significant Drug-Drug Interaction between Cannabidiol and Tacrolimus.

Am J Transplant 2019 Apr 23. Epub 2019 Apr 23.

Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Cannabidiol (CBD), a major purified non-psychoactive component of cannabis with anticonvulsant properties, was approved by the Food and Drug Administration in June 2018 as an adjuvant treatment for refractory epilepsy (Epidiolex; GW Pharmaceuticals). CBD is metabolized by CYP3A4 and CYP2C19 with a growing body of evidence suggesting it is also a potent inhibitor of these pathways. We report for the first time a significant drug-drug interaction between the purified CBD product and tacrolimus. Read More

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http://dx.doi.org/10.1111/ajt.15398DOI Listing

Substitution of an Internal Disulfide Bridge in Human Insulin by a Diselenide Enhances its Foldability and Stability.

Chemistry 2019 Apr 23. Epub 2019 Apr 23.

The Hebrew University of Jerusalem, Institute of Chemistry, Edmond J. Safra Campus, Givat Ram, 91904, Jerusalem, ISRAEL.

Insulin analogs exemplify the utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient due to competing disulfide pairing and aggregation. To overcome these limitations, we envisioned an alternative approach: pairwise substitution of cysteine residues by selenocysteine (Sec, U). Read More

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http://dx.doi.org/10.1002/chem.201900892DOI Listing

The pattern of cell-to-cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells.

Cancer Sci 2019 Apr 23. Epub 2019 Apr 23.

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China.

microRNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of microRNA, which exerts biological effects on tumor cells. However, the length of microRNA that can pass through certain gap junctions that are composed of specific connexin remains unknown. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.14029
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http://dx.doi.org/10.1111/cas.14029DOI Listing
April 2019
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An integrated experimental and physiologically based pharmacokinetic modeling study of penicillin G in heavy sows.

J Vet Pharmacol Ther 2019 Apr 23. Epub 2019 Apr 23.

Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas.

Penicillin G is widely used in food-producing animals at extralabel doses and is one of the most frequently identified violative drug residues in animal-derived food products. In this study, the plasma pharmacokinetics and tissue residue depletion of penicillin G in heavy sows after repeated intramuscular administrations at label (6.5 mg/kg) and 5 × label (32. Read More

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http://dx.doi.org/10.1111/jvp.12766DOI Listing

Pharmacogenomics-Driven Prediction of Antidepressant Treatment Outcomes: A Machine Learning Approach with Multi-Trial Replication.

Clin Pharmacol Ther 2019 Apr 23. Epub 2019 Apr 23.

Dept. of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL.

We set out to determine whether machine learning-based algorithms that included functionally validated pharmacogenomic biomarkers joined with clinical measures could predict selective serotonin reuptake inhibitor (SSRI) remission/response in patients with major depressive disorder (MDD). We studied 1,030 Caucasian MDD outpatients treated with citalopram/escitalopram in the PGRN-AMPS (n = 398), STAR*D (n = 467), and ISPC (n = 165) trials. GWAS for PGRN-AMPS plasma metabolites associated with SSRI response (serotonin) and baseline MDD severity (kynurenine) identified SNPs in DEFB1, ERICH3, AHR, and TSPAN5 that we tested as predictors. Read More

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http://dx.doi.org/10.1002/cpt.1482DOI Listing

Short-term, low-dose fluoxetine prevents oestrous cycle-linked increase in anxiety-like behaviour in female rats.

J Psychopharmacol 2019 Apr 23:269881119841833. Epub 2019 Apr 23.

2 Instituto de Neurociências e Comportamento, Avenida do Café 2450, Ribeirão Preto, SP, Brazil.

Background And Aims: We sought a robust behavioural test that evoked increased anxiety-like behaviour during the late dioestrus phase of the oestrous cycle (similar to the premenstrual period in women) and tested whether this could be prevented by acute low-dose fluoxetine (FLX).

Methods: Female Wistar rats in different stages of their cycle were exposed to four different tests of anxiety-like behaviour.

Results: No oestrous cycle differences were detected in fear potentiated startle or conditioned freezing to an aversive context. Read More

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http://dx.doi.org/10.1177/0269881119841833DOI Listing

Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients: identification of gaps in knowledge and data.

Crit Rev Toxicol 2019 Apr 23:1-14. Epub 2019 Apr 23.

a Integrative Toxicology , Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden.

Computational modeling together with experimental data are essential to assess the risk for particulate matter mediated lung toxicity and to predict the efficacy, safety and fate of aerosolized drug molecules used in inhalation therapy. In silico models are widely used to understand the deposition, distribution, and clearance of inhaled particles and aerosols in the human lung. Exacerbations of chronic obstructive pulmonary disease (COPD) have been reported due to increased particulate matter related air pollution episodes. Read More

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http://dx.doi.org/10.1080/10408444.2019.1584153DOI Listing

Opposite alterations of endothelin-1 in lung and pulmonary artery mirror gene expression of bone morphogenetic protein receptor 2 in experimental pulmonary hypertension.

Exp Lung Res 2019 Apr 23:1-12. Epub 2019 Apr 23.

a Department of Pharmacology and Toxicology, Faculty of Pharmacy , Comenius University in Bratislava , Bratislava , Slovakia.

Aim Of The Study: Endothelin-1 (ET-1) overexpression was suggested to play a role in pulmonary hypertension (PH). However, the roles of ET-1 in early stages of PH remain unexplored. We examined the expression of ET-1 and relevant disease progression markers in the pulmonary artery and the lungs during the development of PH induced by monocrotaline (MCT). Read More

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https://www.tandfonline.com/doi/full/10.1080/01902148.2019.1
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http://dx.doi.org/10.1080/01902148.2019.1605426DOI Listing
April 2019
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MicroRNA-31 Negatively Regulates Interleukin-34 Expression In Vitro.

Immunol Invest 2019 Apr 23:1-11. Epub 2019 Apr 23.

d Department of Basic and Clinical Pharmacology, School of Pharmacy , Anhui Medical University , Hefei , Anhui Province , P.R.China.

Interleukin-34 (IL-34) is a recently discovered cytokine that promotes tissue macrophage maturation and differentiation. We previously found that 1α,25-Dihydroxyvitamin D3 up-regulated IL-34 expression in SH-SY5Y neural cells. However, whether microRNA regulates IL-34 expression is not completely clear. Read More

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http://dx.doi.org/10.1080/08820139.2019.1578230DOI Listing

Methotrexate treatment in rheumatoid arthritis and elevated liver enzymes: A long-term follow-up of predictors, surveillance, and outcome in clinical practice.

Int J Rheum Dis 2019 Apr 22. Epub 2019 Apr 22.

Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden.

Aim: To assess predictors of alanine aminotransferase (ALT) elevation in methotrexate (MTX) treated rheumatoid arthritis (RA) patients, and to describe the monitoring of liver enzymes, including handling and outcome of elevated ALT.

Methods: All RA patients starting MTX in January, 2005 to April, 2013 at a rheumatology clinic, (Uppsala University Hospital, Sweden) were identified from electronic medical records. Clinical and laboratory data were obtained from medical records, supplemented by telephone interviews. Read More

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http://dx.doi.org/10.1111/1756-185X.13576DOI Listing

Activation of Mast Cells Mediates Inflammatory Response in Psoriasis: Potential New Therapeutic Approach with IL-37.

Dermatol Ther 2019 Apr 22:e12943. Epub 2019 Apr 22.

Department of Microbiology and Infectious Diseases, Aristotle University of Thessaloniki, Macedonia, Greece.

Psoriasis (PS) is an autoimmune disorder characterized by chronic inflammatory skin immune-mediated disease which occurs in 2-4% of the worldwide population. PS is associated with an increased risk of cardiovascular disease and depression, and 30% of PS patients are affected with psoriatic arthritis. PS presents excessive keratinocyte proliferation, abnormal differentiation, and elevated mast cell (MC) number. Read More

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http://dx.doi.org/10.1111/dth.12943DOI Listing

Ethanol induces maladaptive impulse control and decreased seeking behaviors in mice.

Addict Biol 2019 Apr 22:e12754. Epub 2019 Apr 22.

Neuroscience Program, Mayo Clinic College of Medicine Rochester, Rochester, Minnesota.

Waiting impulsivity is a risk factor for many psychiatric disorders including alcohol use disorder (AUD). Highly impulsive individuals are vulnerable to alcohol abuse. However, it is not well understood whether chronic alcohol use increases the propensity for impulsive behavior. Read More

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http://dx.doi.org/10.1111/adb.12754DOI Listing

Endothelium-dependent and endothelium-independent effects of 1-nitro-2-propylbenzene on rat aorta.

Fundam Clin Pharmacol 2019 Apr 22. Epub 2019 Apr 22.

Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1-nitro-2-propylbenzene (NPB), a nitro compound containing the NO in the aromatic ring. In aorta precontracted with KCl, NPB (1-3000 μM) induced full endothelium-independent relaxation. Read More

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http://dx.doi.org/10.1111/fcp.12475DOI Listing

A Novel Dipeptide Ligand of TSPO.

Dokl Biochem Biophys 2019 May 22;484(1):17-20. Epub 2019 Apr 22.

Zakusov Research Institute of Pharmacology, 125315, Moscow, Russia.

On the basis of the first dipeptide ligand of TSPO, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), which was obtained by us earlier, we synthesized a new dipeptide, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102). GD-102 exhibited anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD-102 was one order of magnitude lower than that of GD-23. Read More

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http://dx.doi.org/10.1134/S1607672919010046DOI Listing

Recombinant Production and Structure-Function Study of the Ts1 Toxin from the Brazilian Scorpion Tityus serrulatus.

Dokl Biochem Biophys 2019 May 22;484(1):9-12. Epub 2019 Apr 22.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.

An effective bacterial system for the production of β-toxin Ts1, the main component of the Brazilian scorpion Tityus serrulatus venom, was developed. Recombinant toxin and its N-labeled analogue were obtained via direct expression of synthetic gene in Escherichia coli with subsequent folding from the inclusion bodies. According to NMR spectroscopy data, the recombinant toxin is structured in an aqueous solution and contains a significant fraction of β-structure. Read More

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http://dx.doi.org/10.1134/S1607672919010034DOI Listing

Patients with atopy exhibit reduced cortisol awakening response but not cortisol concentrations during the rest of the day.

Immunol Res 2019 Apr 22. Epub 2019 Apr 22.

Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia.

It has been documented that cortisol release in response to acute stressors is reduced in patients with atopic dermatitis, allergic rhinitis, and other atopic diseases compared to that in healthy subjects. We aimed to test the hypothesis that atopic patients exert reduced salivary cortisol awakening response (CAR) in comparison with healthy subjects. The hypothesis was tested on a stressful and a relax day selected subjectively. Read More

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http://dx.doi.org/10.1007/s12026-019-09076-wDOI Listing

(3R, 7R)-7-Acetoxyl-9-Oxo-de-O-Methyllasiodiplodin, a Secondary Metabolite of Penicillium Sp., Inhibits LPS-Mediated Inflammation in RAW 264.7 Macrophages through Blocking ERK/MAPKs and NF-κB Signaling Pathways.

Inflammation 2019 Apr 23. Epub 2019 Apr 23.

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, 264005, Shandong, People's Republic of China.

Twelve polyketones were isolated from the fermentation broth of Penicillium sp., including six new compounds (supplementary material). Penicillium sp. Read More

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http://dx.doi.org/10.1007/s10753-019-01009-xDOI Listing

Current status of site-specific cancer registry system for the clinical researches: aiming for future contribution by the assessment of present medical care.

Int J Clin Oncol 2019 Apr 22. Epub 2019 Apr 22.

Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Background: The current status of site-specific cancer registry has not been elucidated, but sufficient system is found in some societies. The purpose of this study was to clear the present condition of site-specific cancer registries in Japan and to suggest for the improvement.

Methods: The questionnaire was conducted by the study group of the Ministry of Health, Labor, and Welfare. Read More

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http://dx.doi.org/10.1007/s10147-019-01434-wDOI Listing

Dopaminergic Therapeutics in Multiple Sclerosis: Focus on Th17-Cell Functions.

J Neuroimmune Pharmacol 2019 Apr 23. Epub 2019 Apr 23.

Laboratory of Clinical Immunology, National Research Center Institute of Immunology of the Federal Medical-Biological Agency, 115478, Moscow, Russia.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with an autoimmune mechanism of development. Currently, one of the most promising directions in the study of MS pathogenesis are the neuroimmune interactions. Dopamine is one of the key neurotransmitters in CNS. Read More

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http://dx.doi.org/10.1007/s11481-019-09852-3DOI Listing

SN-38, the active metabolite of irinotecan, inhibits the acute inflammatory response by targeting toll-like receptor 4.

Cancer Chemother Pharmacol 2019 Apr 22. Epub 2019 Apr 22.

Department of Physiology and Pharmacology, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará, Rua Cel Nunes de Melo, 1127, Rodolfo Teófilo, Fortaleza, Ceará, 60430-270, Brazil.

Purpose: Anticancer-drug efficacy seems to involve the direct interaction with host immune cells. Although topoisomerase I (Top I) inhibitors have been suggested to block LPS-evoked inflammation, the interaction between these drugs and toll-like receptor 4 (TLR4) is unaddressed.

Methods: SN-38, the active metabolite of the Top I inhibitor irinotecan, and TLR4 interaction was assessed using the in vitro luciferase nuclear factor-κB reporter assay, neutrophil migration to murine air-pouch, in silico simulation, and the thermal shift assay (TSA). Read More

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http://dx.doi.org/10.1007/s00280-019-03844-zDOI Listing

High-fat diet promotes adrenaline production by visceral adipocytes.

Eur J Nutr 2019 Apr 22. Epub 2019 Apr 22.

Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, Alameda Prof Hernâni Monteiro, 4200-319, Porto, Portugal.

Purpose: Catecholamines (CA) play a major role in metabolism and immune response. Recent reports showing adipose tissue can synthetize CA enlighten new roles for these amines in obesity. This study aimed to evaluate the expression of both tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) and CA content along preadipocytes differentiation, under normal and obesigenic conditions. Read More

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http://link.springer.com/10.1007/s00394-019-01971-0
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http://dx.doi.org/10.1007/s00394-019-01971-0DOI Listing
April 2019
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Letter to the Editor on Managing Pathologic Scars by Injecting Auto-Cross-Linked Hyaluronic Acid: A Preliminary Prospective Clinical Study.

Aesthetic Plast Surg 2019 Apr 22. Epub 2019 Apr 22.

Wuxi Clinical Medicine School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Wuxi, 214041, China.

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http://dx.doi.org/10.1007/s00266-019-01377-7DOI Listing

The Meta VCI Map consortium for meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping: Design and multicenter pilot study.

Alzheimers Dement (Amst) 2019 Dec 12;11:310-326. Epub 2019 Apr 12.

Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.

Introduction: The Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.

Methods: Cohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. Read More

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http://dx.doi.org/10.1016/j.dadm.2019.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465616PMC
December 2019

Production and evaluation of mono- and di-rhamnolipids produced by VM011.

Data Brief 2019 Jun 3;24:103890. Epub 2019 Apr 3.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati 781032, Assam, India.

Rhamnolipids are amphiphilic compounds secreted by bacteria and possess the emulsification ability. Emulsification ability makes microbial surfactants an excellent candidate for assisting in the breakdown and removal of oil spills. Rhamnolipids have been demonstrated for their antibacterial and antifungal activities. Read More

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http://dx.doi.org/10.1016/j.dib.2019.103890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461592PMC

Abdominal Ultrasound for the Diagnosis of Tuberculosis Among Human Immunodeficiency Virus-Positive Inpatients With World Health Organization Danger Signs.

Open Forum Infect Dis 2019 Apr 7;6(4):ofz094. Epub 2019 Apr 7.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, South Africa.

Background: Studies of the value of abdominal ultrasound for diagnosing human immunodeficiency virus (HIV)-associated tuberculosis have major limitations.

Methods: We conducted a prospective study of HIV-positive inpatients with cough and World Health Organization danger signs. The reference standard was positive culture from any site. Read More

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https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofz09
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http://dx.doi.org/10.1093/ofid/ofz094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469434PMC
April 2019
1 Read

Preconditioning of Mesenchymal Stem Cells with Non-Toxic Concentration of Hydrogen Peroxide Against Oxidative Stress Induced Cell Death: The Role of Hypoxia-Inducible Factor-1.

Adv Pharm Bull 2019 Feb 21;9(1):76-83. Epub 2019 Feb 21.

Razi Drug Research Center, Department of Pharmacology, School of Medicine, Iran University of Medical Science, Tehran, Iran.

To investigate the protective effect of preconditioning with non-toxic dose of hydrogen peroxide (HO) as a possible cell signaling molecule, against cell death induced by toxic concentration of HO or by serum deprivation in human Wharton's jelly-derived mesenchymal stem cells (HWJ-MSCs) and underlying mechanisms. HWJ-MSCs were isolated and identified using flow cytometry. After finding non-toxic concentration of HO, cells preconditioning was performed by HO (20 μM) for 12 h and cell tolerance against serum deprivation or toxic levels of HO was assayed by MTT test. Read More

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http://dx.doi.org/10.15171/apb.2019.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468218PMC
February 2019

Metformin: Ongoing Journey with Superdrug Revolution.

Adv Pharm Bull 2019 Feb 21;9(1):1-4. Epub 2019 Feb 21.

Faculty of Science and Technology, Shendi University, Shendi, Nher Anile, Sudan.

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http://dx.doi.org/10.15171/apb.2019.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468224PMC
February 2019

Acute oral toxicity evaluation of extracts of in wister albino rats as per OECD 425 TG.

Toxicol Rep 2019 4;6:321-328. Epub 2019 Apr 4.

Department of Pharmacology, College of Pharmaceutical Sciences, Dayananda Sagar University, Shavige Malleshwara Hills, Kumaraswamy Layout, Bengaluru, Karnataka, 560078, India.

(Family: Apiaceae) is a medicinal plant and is been a part of traditional cuisine. Hence, an acute toxicity study was performed to confirm its safety profile. Female rats (n=5) were randomly divided into 5 groups. Read More

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http://dx.doi.org/10.1016/j.toxrep.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460325PMC

Cell culture conditions affect the ability of high content imaging assay to detect drug-induced changes in cellular parameters in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Toxicol Rep 2019 28;6:305-320. Epub 2019 Mar 28.

Department of Safety and Exploratory Pharmacology, Safety Assessment and Laboratory Animal Resources, MRL, Merck & Co., Inc, West Point, PA, USA.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are widely used for drug safety and efficacy testing with various techniques, including high content imaging (HCI). Upon drug treatment, a significant number of hiPSC-CMs grown in regular 96-well plates coated with fibronectin detached from the bottom of the plate, complicating data acquisition. Several cell culture configurations were tested to improve cell adherence, and the effects of these configurations on total cell number, separation of feature values between the negative (DMSO 0. Read More

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http://dx.doi.org/10.1016/j.toxrep.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460330PMC

The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis.

Aging Dis 2019 Apr 1;10(2):419-428. Epub 2019 Apr 1.

1School of Medicine and Public Health, The University of Newcastle, Callaghan, NSW, Australia.

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Read More

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http://www.aginganddisease.org/EN/10.14336/AD.2018.0601
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http://dx.doi.org/10.14336/AD.2018.0601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457057PMC
April 2019
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Deficiency of Yes-Associated Protein Induces Cataract in Mice.

Aging Dis 2019 Apr 1;10(2):293-306. Epub 2019 Apr 1.

2The Brain Science Center, Beijing Institute of Basic Medical Sciences, Beijing 100850, China.

Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cataract. Histologically, Yap deficient lens show fewer epithelial cells, retention of nuclei and accumulation of morgagnian globules in the transitional zone and the posterior area. Read More

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http://www.aginganddisease.org/EN/10.14336/AD.2018.0910
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http://dx.doi.org/10.14336/AD.2018.0910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457047PMC
April 2019
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Involvement of the MiR-181b-5p/HMGB1 Pathway in Ang II-induced Phenotypic Transformation of Smooth Muscle Cells in Hypertension.

Aging Dis 2019 Apr 1;10(2):231-248. Epub 2019 Apr 1.

1Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha 410008, China.

Phenotypic transformation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling in hypertension. High mobility group box-1 (HMGB1) has been reported to be involved in several pathogenic processes including VSMC proliferation and migration. The present study was designed to determine the role of HMGB1 in VSMC phenotypic transformation in hypertension. Read More

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http://dx.doi.org/10.14336/AD.2018.0510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457049PMC

Influence of Environment and Lifestyle on Incidence and Progress of Amyotrophic Lateral Sclerosis in A German ALS Population.

Aging Dis 2019 Apr 1;10(2):205-216. Epub 2019 Apr 1.

1Department of Neurology, Hannover Medical School, Germany.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. Read More

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http://dx.doi.org/10.14336/AD.2018.0327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457054PMC

Methodology of drug screening and target identification for new necroptosis inhibitors.

J Pharm Anal 2019 Apr 27;9(2):71-76. Epub 2018 Nov 27.

Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.

Apoptosis has been considered as the only form of regulated cell death for a long time. However, a novel form of programmed cell death called necroptosis was recently reported. The process of necroptosis is regulated and plays a critical role in the occurrence and development of multiple human diseases. Read More

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http://dx.doi.org/10.1016/j.jpha.2018.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460297PMC

Stakeholder driven development of a multi-criteria decision analysis tool for purchasing off-patent pharmaceuticals in Kuwait.

J Pharm Policy Pract 2019 16;12. Epub 2019 Apr 16.

Syreon Research Institute, Budapest, Hungary.

Background: In Kuwait, the government is planning to improve the specifications for purchase of medicine and to improve the tendering system intending to slow the growth of the expenditure for medicine and to improve the sustainability of the healthcare system. Multiple Criteria Decision Analysis (MCDA) is a method which can help to assess multiple and sometimes conflicting criteria in the evaluation of the available alternatives. The objective of this initiative was to develop collaboratively a MCDA tool which is locally relevant, and which could be used to improve the use of performance indicators in the purchasing of off-patent pharmaceuticals. Read More

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https://joppp.biomedcentral.com/articles/10.1186/s40545-019-
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http://dx.doi.org/10.1186/s40545-019-0171-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466779PMC
April 2019
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Retinal alterations in a pre-clinical model of an autism spectrum disorder.

Mol Autism 2019 15;10:19. Epub 2019 Apr 15.

3Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, Av. Prof. Lineu Prestes, 1524, São Paulo, SP 05508-000 Brazil.

Background: Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Read More

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http://dx.doi.org/10.1186/s13229-019-0270-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466731PMC

Disruption of endocytosis through chemical inhibition of clathrin heavy chain function.

Nat Chem Biol 2019 Apr 22. Epub 2019 Apr 22.

Department of Plant Biotechnology and Bioinformatics, Ghent University, Ghent, Belgium.

Clathrin-mediated endocytosis (CME) is a highly conserved and essential cellular process in eukaryotic cells, but its dynamic and vital nature makes it challenging to study using classical genetics tools. In contrast, although small molecules can acutely and reversibly perturb CME, the few chemical CME inhibitors that have been applied to plants are either ineffective or show undesirable side effects. Here, we identify the previously described endosidin9 (ES9) as an inhibitor of clathrin heavy chain (CHC) function in both Arabidopsis and human cells through affinity-based target isolation, in vitro binding studies and X-ray crystallography. Read More

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http://dx.doi.org/10.1038/s41589-019-0262-1DOI Listing

Utility of ctDNA to support patient selection for early phase clinical trials: the TARGET study.

Nat Med 2019 Apr 22. Epub 2019 Apr 22.

Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, Manchester, UK.

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. Read More

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http://dx.doi.org/10.1038/s41591-019-0380-zDOI Listing

Organ-specific metastases obtained by culturing colorectal cancer cells on tissue-specific decellularized scaffolds.

Nat Biomed Eng 2018 Jun 23;2(6):443-452. Epub 2018 Apr 23.

Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Metastatic disease remains the primary cause of mortality in cancer patients. Yet the number of available in vitro models to study metastasis is limited by challenges in the recapitulation of the metastatic microenvironment in vitro, and by difficulties in maintaining colonized-tissue specificity in the expansion and maintenance of metastatic cells. Here, we show that decellularized scaffolds that retain tissue-specific extracellular-matrix components and bound signalling molecules enable, when seeded with colorectal cancer cells, the spontaneous formation of three-dimensional cell colonies that histologically, molecularly and phenotypically resemble in vivo metastases. Read More

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http://www.nature.com/articles/s41551-018-0231-0
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http://dx.doi.org/10.1038/s41551-018-0231-0DOI Listing
June 2018
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Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation.

Nat Chem 2019 Apr 22. Epub 2019 Apr 22.

Center for Biopharmaceuticals, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Staphylococci secrete autoinducing peptides (AIPs) as signalling molecules to regulate population-wide behaviour. AIPs from non-Staphylococcus aureus staphylococci have received attention as potential antivirulence agents to inhibit quorum sensing and virulence gene expression in the human pathogen Staphylococcus aureus. However, only a limited number of AIP structures from non-S. Read More

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http://dx.doi.org/10.1038/s41557-019-0256-3DOI Listing

Modified Ucn2 Peptide Acts as an Insulin Sensitizer in Skeletal Muscle of Obese Mice.

Diabetes 2019 Apr 22. Epub 2019 Apr 22.

Department of Physiology and Pharmacology, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden

The neuropeptide urocortin 2 (Ucn2) and its receptor corticotropin releasing hormone receptor 2 (CRHR2) are highly expressed in skeletal muscle and play a role in regulating energy balance and glucose metabolism. We investigated a modified Ucn2 peptide as a potential therapeutic agent for the treatment of obesity and insulin resistance, with a specific focus on skeletal muscle. High fat-fed mice (C57Bl/6J) were injected daily with a PEGylated Ucn2 peptide (Compound A) at 0. Read More

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http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db18
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http://dx.doi.org/10.2337/db18-1237DOI Listing
April 2019
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The Microbiota-Produced -Formyl Peptide fMLF Promotes Obesity-Induced Glucose Intolerance.

Diabetes 2019 Apr 22. Epub 2019 Apr 22.

Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

The composition of the gastrointestinal (GI) microbiota and associated metabolites changes dramatically with diet and the development of obesity. Although many correlations have been described, specific mechanistic links between these changes and glucose homeostasis remain to be defined. Here we show that blood and intestinal levels of the microbiota-produced formyl peptide, formyl-methionyl-leucyl-phenylalanine (fMLF), are elevated in high fat diet (HFD)-induced obese mice. Read More

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http://dx.doi.org/10.2337/db18-1307DOI Listing
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