Are Patients With Schizophrenia Spectrum Disorders More Prone to Manifest Nocebo-Like-Effects? A Meta-Analysis of Adverse Events in Placebo Groups of Double-Blind Antipsychotic Trials
Conclusion: These results suggest that the AEs in placebo arms of clinical trials of antipsychotic medications were substantial. Importantly, a higher level of psychiatric symptomatology makes SCD patients more prone to express AEs, thus contributing to possible drop-outs and to a lower adherence to treatments. These findings are in accordance with the expectation theory of placebo and nocebo effects. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Editorial: Novel Approaches to the Neuropharmacology of Mood Disorders
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Beyond the Activity-Based Anorexia Model: Reinforcing Values of Exercise and Feeding Examined in Stressed Adolescent Male and Female Mice
This study shows that the ABA model does not specifically capture running and feeding drives, i.e. components known to be affected in AN. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Sodium Dichloroacetate Stimulates Angiogenesis by Improving Endothelial Precursor Cell Function in an AKT/GSK-3 β/Nrf2 Dependent Pathway in Vascular Dementia Rats
Sodium dichloroacetate (DCA) is a mitochondrial pyruvate dehydrogenase kinase inhibitor, and has been shown to display vasoprotective effects in chronic ischemic stroke. The purpose of this study was to evaluate the therapeutic effect of DCA on vascular dementia and endothelial progenitor cell (EPC)-mediated angiogenesis. After cerebral ischemia-reperfusion in rats, DCA was administered continuously for 21 days; following which, histological analysis and cognitive functional tests were conducted. Rat bone marrow-derived endothelial progenitor cells (EPCs) were isolated, their function and quantity were measured, and the ef...
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Elucidation of the Differences in Cinobufotalin ’s Pharmacokinetics Between Normal and Diethylnitrosamine-Injured Rats: The Role of P-Glycoprotein
Cinobufotalin is one of the major anti-tumor components isolated from toad venom and has been used in the clinical therapy of hepatocellular carcinoma (HCC), known as Cinobufacini injection. However, the pharmacokinetic (PK) behaviors of cinobufotalin in vivo with hepatocellular carcinoma are still unknown. Hence, we have established a HCC model in Sprague Dawley (SD) rats induced by diethylnitrosamine (DEN), named as DEN-injured rats. Then, we developed and validated a sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify cinobufotalin in rat plasma. This UPL...
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Dysregulation of Mesenchymal Cell Survival Pathways in Severe Fibrotic Lung Disease: The Effect of Nintedanib Therapy
Impaired apoptotic clearance of myofibroblasts can result in the continuous expansion of scar tissue during the persistent injury in the lung. However, the molecular and cellular mechanisms underlying the apoptotic clearance of multiple mesenchymal cells including fibrocytes, fibroblasts and myofibroblasts in severe fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) remain largely unknown. We analyzed the apoptotic pathways activated in mesenchymal cells of IPF and in a mouse model of TGFα-induced pulmonary fibrosis. We found that fibrocytes and myofibroblasts in fibrotic lung lesions have acquired re...
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Reduced Alcohol Seeking and Withdrawal Symptoms in Mice Lacking the BDNF Receptor SorCS2
Alcohol use disorder (AUD) is characterized by repetitive and uncontrolled intake of alcohol with severe consequences for affected individuals, their families and society as a whole. Numerous studies have implicated brain-derived neurotrophic factor (BDNF) activity in the neurobiology underlying AUD. The BDNF signaling mechanism is complex and depends on two receptor systems, TrkB and p75NTR, which appear to have opposite effects on alcohol seeking behavior in animal models. We recently discovered that the sortilin-related receptor SorCS2 forms complexes with both TrkB and p75NTR and is important for BDNF activity in the d...
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Computational Advances in Drug Safety: Systematic and Mapping Review of Knowledge Engineering Based Approaches
In conclusion, we argue that efficiently addressing DS data analytics and management challenges in order to establish a continuous learning DS system, requires the introduction of high-throughput KE-based methods for effective knowledge discovery and management. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Monoaminergic System Modulation in Depression and Alzheimer ’s Disease: A New Standpoint?
The prevalence of depression is dramatically increased and it has been esteemed that over 300 million people suffer from depression all over the world. Depression is highly comorbid with many central and peripheral disorders. In this regard, depressive states have been associated with the development of neurological disorders such as Alzheimer’s disease (AD). Accordingly, depression is a risk factor for AD and depressive symptomatology is common in pre-clinical AD representing an early manifestation of this disease. Neuropsychiatric symptoms may represent prodromal symptoms of dementia deriving from neurobiological c...
Source: Frontiers in Pharmacology - May 17, 2019 Category: Drugs & Pharmacology Source Type: research

Effects of PARP-1 Deficiency and Histamine H4 Receptor Inhibition in an Inflammatory Model of Lung Fibrosis in Mice
Pulmonary fibrosis is the most frequent form of interstitial lung disease. Effective therapies are not yet available; novel therapeutic approaches are needed for counteracting fibrosis. Poly(ADP-ribose) polymerase is a family of enzymes, involved in DNA repair and cell apoptosis. PARP-1 deficient mice exhibited reduced lung fibrosis in response to bleomycin treatment compared to wild-type controls. Histamine H4 receptors (H4Rs) have been identified as a new target for inflammatory and immune disorders and H4R ligands reduced inflammation and oxidative stress in lung tissue. The aim of the study was to evaluate the invol...
Source: Frontiers in Pharmacology - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Glycyrrhetinic Acid Maintains Intestinal Homeostasis via HuR
Glycyrrhetinic acid (GA) is one of the main components for the traditional medicine of licorice, which can synchronize and promote effects of other medicines in the traditional prescription. In this paper we found GA could promote IEC-6 cell proliferation, rescue the proliferative inhibition caused by DFMO, decrease the apoptotic rate, and reverse the delay in restitution after wounding caused by DMFO in IEC-6 cells via HuR. To be noted, GA failed to promote proliferation and to suppress apoptosis after silencing HuR by siRNA in IEC-6 cells. Furthermore, with the model of small intestinal organoids developed from intestina...
Source: Frontiers in Pharmacology - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Enhanced Inhibition of Tumorigenesis Using Combinations of miRNA-Targeted Therapeutics
The search for effective strategies to inhibit tumorigenesis remains one of the most relevant scientific challenges. Among the most promising approaches is the direct modulation of the function of short non-coding RNAs, particularly miRNAs. These molecules are propitious targets for anticancer therapy, since they perform key regulatory roles in a variety of signaling cascades related to cell proliferation, apoptosis, migration, and invasion. The development of pathological states is often associated with deregulation of miRNA expression. The present review describes in detail the strategies aimed at modulating miRNA activi...
Source: Frontiers in Pharmacology - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Relevance of Autophagy Induction by Gastrointestinal Hormones: Focus on the Incretin-Based Drug Target and Glucagon
The biology of autophagy in health and disease conditions has been intensively analyzed for decades. Several potential interventions can induce autophagy in preclinical research; however, none of these interventions are ready for translation to clinical practice yet. The topic of the current review is the molecular regulation of autophagy by glucagon, glucagon-like peptide (GLP)-1 and the GLP-1-degrading enzyme DPP-4. Glucagon is a well-known polypeptide that induces autophagy. In contrast, GLP-1 has been shown to inhibit glucagon secretion; GLP-1 also has been related to the induction of autophagy. DPP-4 inhibitors can in...
Source: Frontiers in Pharmacology - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Synergistic Effect of Retinoic Acid Polymeric Micelles and Prodrug for the Pharmacodynamic Evaluation of Tumor Suppression
This study suggested the potential of pluronic ATRA, which can be used as an anticancer agent in combination therapy against solid tumor. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 16, 2019 Category: Drugs & Pharmacology Source Type: research

Medical Cost of Colorectal Cancer Services in Serbia Between 2014 and 2017: National Data Report
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 15, 2019 Category: Drugs & Pharmacology Source Type: research

The Effect of Once-Daily Gabapentin Extended Release Formulation in Patients With Postamputation Pain
Objectives: To compare gabapentin extended-release, a gastro-retentive formulation, in relieving postamputation pain among gabapentin-experienced and gabapentin-naive patients. Design: Open-labeled pilot study Subjects: Sixteen patients with postamputation pain (8 patients in the gabapentin-experienced and 8 patients in the gabapentin-naive groups) Methods: Patients were started on gabapentin extended-release and followed up for 8 weeks. Patients reported their pain severity during rest and movement using a numeric rating scale (NRS), interference of pain with daily activities using the modified brief pain inventory (MB...
Source: Frontiers in Pharmacology - May 15, 2019 Category: Drugs & Pharmacology Source Type: research

METTL3/m6A/miRNA-873-5p Attenuated Oxidative Stress and Apoptosis in Colistin-Induced Kidney Injury by Modulating Keap1/Nrf2 Pathway
Nephrotoxicity of colistin is the major factor limiting its clinical application. However, the exact mechanism of colistin-induced nephrotoxicity is still elusive. N6-Methyladenosine (m6A) modification has been implicated in many biological processes, however, its role in colistin induced nephrotoxicity needs to be elucidated. Mouse renal tubular epithelial cells (mTRECs) were treated with 200 μM colistin with or without METTL3 transient overexpression. Cells injury, m6A assay, oxidative stress and apoptosis were examined. Modifications of m6A are decreased after colistin treatment in mRTECs. METTL3 is the major factor ...
Source: Frontiers in Pharmacology - May 15, 2019 Category: Drugs & Pharmacology Source Type: research

Anti-tumor Efficacy Assessment of the Sigma Receptor Pan Modulator RC-106. A Promising Therapeutic Tool for Pancreatic Cancer
Conclusions Overall, our data evidenced that the pan-SR modulator RC-106 is an optimal candidate for in vivo studies in animal models of PC. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

Abscopal Effects in Radio-Immunotherapy —Response Analysis of Metastatic Cancer Patients With Progressive Disease Under Anti-PD-1 Immune Checkpoint Inhibition
Immune checkpoint inhibition (ICI) targeting the programmed death receptor 1 (PD-1) has shown promising results in the fight against cancer. Systemic anti-tumor reactions due to radiation therapy (RT) can lead to regression of non-irradiated lesions (NiLs), termed "abscopal effect" (AbE). Combination of both treatments can enhance this effect. The aim of this study was to evaluate AbEs during anti-PD-1 therapy and irradiation. We screened 168 patients receiving pembrolizumab or nivolumab at our center. Inclusion criteria were start of RT within 1 month after the first or last application of pembrolizumab (2mg/kg...
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

Emerging Fluorescent Molecular Tracers to Guide Intra-Operative Surgical Decision-Making
Fluorescence imaging is an emerging technology that can provide real-time information about the operating field during cancer surgery. Non-specific fluorescent agents, used for the assessment of blood flow and sentinel lymph node detection, have so far dominated this field. However, over the last decade, several clinical studies have demonstrated the great potential of targeted fluorescent tracers to visualize tumor lesions in a more specific way. This has led to an exponential growth in the development of novel molecular fluorescent contrast agents. In this review, the design of fluorescent molecular tracers will be discu...
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

miR-155 in the Resolution of Atherosclerosis
Atherosclerosis is a chronic progressive inflammatory disease where advanced lesions can eventually completely obstruct blood flow resulting in clinical events, such as a myocardial infarction or stroke. Monocytes and macrophages are the dominant biologically active immune cells involved in atherosclerosis disease and play a pivotal role during initiation, progression and regression of disease. Altering macrophage inflammation is critical to induce regression of atherosclerosis and microRNAs (miRs) have emerged as key regulators of the macrophage phenotype. MiRs are small non-coding RNAs that regulate gene expression. ...
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

CYP2J2 ∗7 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients
Chemotherapy induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and the implication of genetic variations. Breast cancer patients (n=249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 hematologic toxicity and reduc...
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

A Single Dose of Baicalin Has No Clinically Significant Effect on the Pharmacokinetics of Cyclosporine A in Healthy Chinese Volunteers
This study investigated the effect of BG on CsA pharmacokinetics. In a two-period study, 16 healthy volunteers received a single 200 mg oral CsA dose alone (reference period) or in combination with 500 mg BG (test period). Pharmacokinetic evaluation of CsA was carried out using non-compartmental analysis (NCA) and population pharmacokinetics (popPK). Treatments were compared using the standard bioequivalence method. Based on NCA, 90% CIs of AUC and Cmax test-to-reference ratios were within bioequivalence boundaries. In the popPK analysis, a two-compartment model (clearance/F 62.8 L/h, central and peripheral volume of distr...
Source: Frontiers in Pharmacology - May 14, 2019 Category: Drugs & Pharmacology Source Type: research

Nanofibrous Scaffolds Support a 3D in vitro Permeability Model of the Human Intestinal Epithelium
In this study, an in vitro model of the human intestinal epithelium was developed by utilizing nanofibers, fabricated using electrospinning, to mimic the structure of the basement membrane. We assessed Caco-2 cell response to these materials and investigated the physiological properties of these cells cultured on the fibrous supports, focusing on barrier integrity and drug-permeability properties. The obtained data illustrate that 2D Caco-2 Transwell® cultures exhibit artificially high trans-epithelial electrical resistance (TEER) compared to cells cultured on the 3D nanofibrous scaffolds which show TEER values similar...
Source: Frontiers in Pharmacology - May 11, 2019 Category: Drugs & Pharmacology Source Type: research

Epoxyeicosatrienoic Acid Analog EET-A Blunts Development of Lupus Nephritis in Mice
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that causes life threatening renal disease and current therapies are limited with serious side-effects. CYP epoxygenase metabolites of arachidonic acid epoxyeicosatrienoic acids (EETs) demonstrate strong anti-inflammatory and kidney protective actions. We investigated the ability of an orally active EET analog, EET-A to prevent kidney injury in a mouse SLE model. Twenty-weeks old female NZBWF1 (SLE) and age-matched NZW/LacJ (Non SLE) were treated with vehicle or EET-A (10 mg/kg/d, p.o.) for 14 weeks and urine and kidney tissues were collected ...
Source: Frontiers in Pharmacology - May 10, 2019 Category: Drugs & Pharmacology Source Type: research

Antithrombin III Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Excessive Autophagy in a Phosphoinositide 3-Kinase/Akt-Dependent Manner
This study showed that AT exhibits a cardioprotective effect by modulating autophagy during I/R in a phosphoinositide 3-kinase/Akt-dependent manner. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 10, 2019 Category: Drugs & Pharmacology Source Type: research

Lavender (Lavandula angustifolia Mill.) Essential Oil Alleviates Neuropathic Pain in Mice With Spared Nerve Injury
Low treatment efficacy represents an important unmet need in neuropathic pain patients and there is an urgent need to develop a more effective pharmacotherapy. An increasing number of patients choose complementary medicine to relieve pain. Lavender essential oil (LEO) is approved by the European Medicines Agency as herbal medicine to relieve anxiety and stress. However, the capability of LEO to relieve other nervous system disorders such as neuropathic pain has never been established. Our work aimed to evaluate the antineuropathic properties of lavender on a spared nerve injury (SNI) model of neuropathic pain in mice. An a...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Theranostics in Interventional Oncology: Versatile Carriers for Diagnosis and Targeted Image-Guided Minimally Invasive Procedures
We are continuously progressing in our understanding of cancer and other diseases and learned how they can be heterogeneous among patients. Therefore, there is an increasing need for accurate characterization of diseases at the molecular level. In parallel, medical imaging and image-guided therapies are rapidly developing fields with new interventions and procedures entering constantly in clinical practice. Theranostics, a relatively new branch of medicine, refers to procedures combining diagnosis and treatment, often based on patient and disease-specific features or molecular markers. Interventional oncology which is at t...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Modulation of the Endocannabinoid System as a Potential Anticancer Strategy
Currently, the involvement of the endocannabinoid system in cancer development and possible options for a cancer-regressive effect of cannabinoids are controversially discussed. In recent decades, a number of preclinical studies have shown that cannabinoids have an anticarcinogenic potential. Therefore, especially against the background of several legal simplifications with regard to the clinical application of cannabinoid-based drugs, an extended basic knowledge about the complex network of the individual components of the endocannabinoid system is required. The canonical endocannabinoid system consists of the endocannabi...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Synergistic Cytotoxicity of Methyl 4-Hydroxycinnamate and Carnosic Acid to Acute Myeloid Leukemia Cells via Calcium-Dependent Apoptosis Induction
In this study, we identified another phenolic compound, methyl 4-hydroxycinnamate (MHC), which among several tested phytochemicals could uniquely cooperate with CA in killing AML cells, but not normal peripheral blood mononuclear cells. Notably, our data revealed striking phenotypical and mechanistic similarities in the apoptotic effects of MHC+CA and CUR+CA on AML cells. Yet, we show that MHC is a non-fluorescent molecule, which is an important technical advantage over CUR that can interfere in various fluorescence-based assays. Collectively, we demonstrated for the first time the antileukemic activity of MHC in combinati...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

The Potential Antipyretic Mechanism of Gardeniae Fructus and Its Heat-Processed Products With Plasma Metabolomics Using Rats With Yeast-Induced Fever
In this study rectal temperature and pyrogenic cytokines were used to evaluate the antipyretic effect of raw and processed GF in rats with dry-yeast-induced pyrexia. Reverse phase and hydrophilic interaction liquid chromatography ultra-high-performance liquid chromatography/mass spectrometry was used to acquire the metabolomics profile of GF, GFP, and GFC in rats with pyrexia. The results showed that the rectal temperature of rats treated with GF, GFP, and GFC was suppressed after 6 h (P (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Developmental Pharmacokinetics and Safety of Ibuprofen and Its Enantiomers in the Conventional Pig as Potential Pediatric Animal Model
Pediatric drug development, especially in disease areas that only affect children, can be stimulated by using juvenile animal models not only for general safety studies, but also to gain knowledge on the pharmacokinetic and pharmacodynamic properties of the drug. Recently, the conventional growing piglet has been suggested as juvenile animal model. However, more studies with different classes of drugs are warranted to make a thorough evaluation whether the juvenile pig might be a suitable preclinical animal model. Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs in human. The present study det...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

All-Trans-Retinoic Acid Suppresses Neointimal Hyperplasia and Inhibits Vascular Smooth Muscle Cell Proliferation and Migration via Activation of AMPK Signaling Pathway
In this study, we found treatment with ATRA significantly reduced neointimal hyperplasia in left common carotid artery ligation mice model. Accordingly, we found that ATRA reduced the cell proliferation of A7r5, a rat VSMC cell line in a dose- and time-dependent manner. Our results also demonstrated that ATRA altered the expression of proliferation-related proteins, including CyclinD1, CyclinD3 and CDK4 in A7r5 cells. ATRA dose-dependently enhanced the phosphorylation level of AMPKα (Thr172) in the left common carotid artery of model mice. Also, the phosphorylation level of AMPKα in A7r5 was significantly incre...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Lipophagy and Alcohol-Induced Fatty Liver
Abstract: This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All three contribute, in part, to alcohol-induced fatty liver (steatosis). Here, our principal focus is on lipid catabolism, specifically the impact of excessive ethanol consumption on lipophagy, which also influences...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Identification of GLPG/ABBV-2737, a Novel Class of Corrector, Which Exerts Functional Synergy With Other CFTR Modulators
The deletion of phenylalanine at position 508 (F508del) in cystic fibrosis transmembrane conductance regulator (CFTR) causes a severe defect in folding and trafficking of the chloride channel resulting in its absence at the plasma membrane of epithelial cells leading to cystic fibrosis. Progress in the understanding of the disease increased over the past decades and led to the awareness that combinations of mechanistically different CFTR modulators are required to obtain meaningful clinical benefit. Today, there remains an unmet need for identification and development of more effective CFTR modulator combinations to improv...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Corrigendum: Ion Channel Targeted Mechanisms of Anti-arrhythmic Chinese Herbal Medicine Xin Su Ning
(Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients
Ventilator-associated pneumonia (VAP), a hospital acquired pneumonia that occurs more than 48 hours after mechanical ventilation, is a common complication of mechanical ventilation with a high mortality rate. VAP can cause patients to have difficulty weaning off the ventilator and to stay in the hospital longer, which results in a huge financial burden to patients and a huge demand for medical resources. Several strategies, such as drugs including chlorhexidine, β-lactam antibiotics and probiotics, have been used to prevent VAP in clinic. The incidence and the mortality rate of VAP have been decreased with the develop...
Source: Frontiers in Pharmacology - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

In vitro and in vivo Metabolism of a Potent Inhibitor of Soluble Epoxide Hydrolase, 1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea
1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (TPPU) is a potent soluble epoxide hydrolase (sEH) inhibitor that is used extensively for modulating inflammation and protecting against hypertension, neuropathic pain and neurodegeneration. Despite its wide use in various animal disease models, the metabolism of TPPU has not been well studied. Herein, we describe the identification of TPPU metabolites using LC-MS/MS strategies. Four metabolites (M1-M4) were identified from rat urine by a sensitive LC-MS/MS method with double precursor ion scans. Their structures were further supported by LC-MS/MS comparison ...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Reimbursement Legislations and Decision Making for Orphan Drugs in Central and Eastern European Countries
Conclusions: In considered countries specific regulations on reimbursement of orphan drugs are valid but in Lithuania and Romania no formal HTA process was employed; in case of some countries higher ICER values for orphans are used. The share of reimbursed orphan drugs varied significantly across the countries, but it was not associated with GDP per capita. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Respiratory Fluoroquinolones Monotherapy vs. β-Lactams With or Without Macrolides for Hospitalized Community-Acquired Pneumonia Patients: A Meta-Analysis
Conclusions Current evidence shows that fluoroquinolone monotherapy has similar efficacy and favorable safety compared with β-lactam with or without macrolide for non-ICU hospitalized CAP patients. Since the limitation of region, quantity and quality of included studies, more RCTs with large scale and high quality are needed to verify the above conclusion. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Efficacy Assessment of Ultrasound Guided Lauromacrogol Injection for Ablation of Benign Cystic and Predominantly Cystic Thyroid Nodules
Background: To assess the efficacy and safeness of ultrasound guided lauromacrogol injection for ablation of benign cystic and predominantly cystic thyroid nodules. Methods: From July 2016 to July 2018, 102 patients with 107 nodules were treated with ultrasound guided lauromacrogol injection for ablation and 43 nodules completed at least 12 months follow-up. Nodules sonographic characteristics, volume changes before and after USG-LIA, and comlications were evaluated. Results: Mean nodule volume decreased from 17.27±20.51ml to 5.35±14.68ml (P50%) was 91.67% in purely cysts and 75.90% in predominantly cystic no...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections
Bacteriophages (BPs) are viruses that can infect and kill bacteria without any negative effect on human or animal cells. For this reason, it is supposed that they can be used, alone or in combination with antibiotics, to treat bacterial infections. In this narrative review, the advantages and limitations of BPs for use in humans will be discussed. PubMed was used to search for all of the studies published from January 2008 to December 2018 using the key words: “bacteriophages” or “phages” and “bacterial infection” or “antibiotic” or “infectious diseases”. More tha...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Asteraceae Plants as Sources of Compounds Against Leishmaniasis and Chagas Disease
Leishmaniasis and Chagas disease cause great impact on social and economic aspects of people living in developing countries. The treatments for these diseases have been based on the same regimen for over 40 year, thus, there is an urgent need for the development of new drugs. In this scenario, Asteraceae plants (a family widely use in folk medicine worldwide) are emerging as interesting sources of new trypanocidal and leishmanicidal compounds. Herein, we provide a non-exhaustive review about the activity of plant-derived products from Asteraceae with inhibitory action towards Leishmania spp. and T. cruzi. Special attention...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Pterostilbene Activates the Nrf2-Dependent Antioxidant Response to Ameliorate Arsenic-Induced Intracellular Damage and Apoptosis in Human Keratinocytes
The NF-E2 p45-related factor 2 (Nrf2), a transcription factor that regulates the cellular adaptive response to oxidative stress, is a target for limiting tissue damage from exposure to environmental toxins, including arsenic. In the current study, we determine whether Pterostilbene (Pts), as a potent activator of Nrf2, has a protective effect on arsenic-induced cytotoxicity and apoptosis in human keratinocytes. Human keratinocytes (HaCaT) or mouse epidermal cells (JB6) were pretreated with Pts for 24 h prior to arsenic treatment. Harvested cells were analyzed by MTT, DCFH-DA, commercial kits, Flow cytometry assay and weste...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF- κB Signal Pathway in the Mouse Hippocampus
In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Suspected Adverse Drug Reactions Related to Breast Cancer Chemotherapy: Disproportionality Analysis of the Brazilian Spontaneous Reporting System
Spontaneous reporting systems may generate a large volume of information in real world conditions with a relatively low cost. Disproportionality measures are useful to indicate and quantify unexpected safety issues associated with a given drug-event pair (signals of disproportionality), based upon differences compared to the background reporting frequency. This cross-sectional study (2008 to 2013) aimed to analyse the feasibility of detecting such signals in the Brazilian Pharmacovigilance Database comprising suspected adverse drug reactions related to the use of doxorubicin, cyclophosphamide, carboplatin, trastuzumab, doc...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

NMDA Receptor Antagonist Effects on Speech-Related Mismatch Negativity and Its Underlying Oscillatory and Source Activity in Healthy Humans
Conclusions: Ketamine-induced impairments in healthy human speech MMNs and their underlying electrocortical mechanisms closely resemble those observed in schizophrenia and support a model of dysfunctional NMDA receptor-mediated neurotransmission of language processing deficits in schizophrenia. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Cost-Effectiveness of Canagliflozin Versus Dapagliflozin Added to Metformin in Patients With Type 2 Diabetes in China
Conclusions: These results suggested that canagliflozin was a cost-saving treatment option compared with dapagliflozin from the perspective of Chinese health care services providers for Chinese patients with T2DM who are inadequately controlled on metformin monotherapy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Momordica charantia, a Nutraceutical Approach for Inflammatory Related Diseases
Momordica charantia, commonly called bitter melon, is a plant belonging to Cucurbitaceae family known for centuries for its pharmacological activities and nutritional properties. Due to the presence of many bioactive compounds, some of which possess potent biological actions, this plant is used in folk medicine all over the world for the treatment of different pathologies, mainly diabetes, but also cancer and other inflammation-associated diseases. It is widely demonstrated that Momordica charantia extracts contribute in lowering glycaemia in patients affected by type 2 diabetes. However, the majority of existing studies o...
Source: Frontiers in Pharmacology - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

The Efflux Mechanism of Fraxetin-O-Glucuronides in UGT1A9-Transfected HeLa Cells: Identification of Multidrug Resistance-Associated Proteins 3 and 4 (MRP3/4) as the Important Contributors
In this study, we aimed to determine the active efflux transporters, including breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), involved in the excretion of fraxetin-O-glucuronides. A chemical inhibitor, MK571 (5 and 20 μM), a pan-MRP inhibitor, led to a significant decrease in excreted G1 (maximal 59.1%) and G2 levels (maximal 42.4%), whereas Ko143 (5 and 20 μM), a selective BCRP inhibitor, caused moderate downregulation of excreted G1 (maximal 29.4%) and G2 (maximal 28.5%). Furthermore, MRP3 silencing resulted in a marked decrease of excretion rates (by 29.1% for G1 and b...
Source: Frontiers in Pharmacology - May 7, 2019 Category: Drugs & Pharmacology Source Type: research