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https://www.readbyqxmd.com/read/28830123/application-of-a-urine-and-hair-validated-lc-ms-ms-method-to-determine-the-effect-of-hair-color-on-the-incorporation-of-25b-nbome-25c-nbome-and-25i-nbome-into-hair-in-the-rat
#1
Lorna A Nisbet, Rafael Venson, Fiona M Wylie, Karen S Scott
NBOMes are a group of new psychoactive substances derived from phenethylamines. Recreational abuse is thought to have begun in 2010 and they are commonly associated with the "club drug" scene. They are administered in liquid form or as blotters due to their high potency. An LC-MS-MS method was validated using Scientific Working Group for Forensic Toxicology parameters for the detection of 25B-, 25C- and 4-iodo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25I-NBOMe) using 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe)-D3 as internal standard for urine and hair...
July 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28830106/digital-pharmacovigilance-and-disease-surveillance-combining-traditional-and-big-data-systems-for-better-public-health
#2
Marcel Salathé
The digital revolution has contributed to very large data sets (ie, big data) relevant for public health. The two major data sources are electronic health records from traditional health systems and patient-generated data. As the two data sources have complementary strengths-high veracity in the data from traditional sources and high velocity and variety in patient-generated data-they can be combined to build more-robust public health systems. However, they also have unique challenges. Patient-generated data in particular are often completely unstructured and highly context dependent, posing essentially a machine-learning challenge...
December 1, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28830049/aerobic-activated-sludge-transformation-of-vincristine-and-identification-of-the-transformation-products
#3
Tina Kosjek, Noelia Negreira, Ester Heath, Miren López de Alda, Damià Barceló
This study aims to identify (bio)transformation products of vincristine, a plant alkaloid chemotherapy drug. A batch biotransformation experiment was set-up using activated sludge at two concentration levels with and without the addition of a carbon source. Sample analysis was performed on an ultra-high performance liquid chromatograph coupled to a high-resolution hybrid quadrupole-Orbitrap tandem mass spectrometer. To identify molecular ions of vincristine transformation products and to propose molecular and chemical structures, we performed data-dependent acquisition experiments combining full-scan mass spectrometry data with product ion spectra...
August 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28830009/humanization-of-jaa-f11-a-highly-specific-anti-thomsen-friedenreich-pancarcinoma-antibody-and-invitro-efficacy-analysis
#4
Swetha Tati, John C Fisk, Julia Abdullah, Loukia Karacosta, Taylor Chrisikos, Padraic Philbin, Susan Morey, Diala Ghazal, Fatma Zazala, Joseph Jessee, Sally Quataert, Stephen Koury, David Moreno, Jing Ying Eng, Vladislav V Glinsky, Olga V Glinskii, Muctarr Sesay, Anthony W Gebhard, Karamveer Birthare, James R Olson, Kate Rittenhouse-Olson
JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11)...
August 19, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28829508/regulation-of-mirnas-on-c-met-protein-expression-in-ovarian-cancer-and-its-implication
#5
H Liu, S-R Li, Q Si
OBJECTIVE: HGF/c-met signal pathway exerts important roles in tumor pathogenesis. The study of c-met related regulatory mechanism provides the basis for finding anti-tumor molecular drugs. MiRNAs can effectively regulate gene expression and work as gene therapy. The identification of miRNAs for c-met regulation and study of related mechanism are of critical importance. MATERIALS AND METHODS: Bioinformatics approach was used to search for possible miRNAs with regulatory functions on c-met gene...
August 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28829421/electroconvulsive-seizures-in-rats-and-fractionation-of-their-hippocampi-to-examine-seizure-induced-changes-in-postsynaptic-density-proteins
#6
Sung-Soo Jang, Han Gil Jeong, Hee Jung Chung
Electroconvulsive seizure (ECS) is an experimental animal model of electroconvulsive therapy, the most effective treatment for severe depression. ECS induces generalized tonic-clonic seizures with low mortality and neuronal death and is a widely-used model to screen anti-epileptic drugs. Here, we describe an ECS induction method in which a brief 55-mA current is delivered for 0.5 s to male rats 200 - 250 g in weight via ear-clip electrodes. Such bilateral stimulation produced stage 4 - 5 clonic seizures that lasted about 10 s...
August 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28829208/emerging-drugs-for-the-treatment-of-benign-prostatic-hyperplasia
#7
Dominique Bs Thomas, Bilal Chughtai, Mitali Kini, Alexis Te
Benign prostatic hyperplasia (BPH) is a common condition affecting over 50% of men as they reach their 5(th) decade of life. This leads to a number of sequelae such as lower urinary tract symptoms, urinary retention and a decrease in quality of life. Currently, the available treatments for BPH are alpha blockers and 5-alpha reductase inhibitors. Clinical studies have demonstrated these medical options are effective in alleviating a patient's symptoms, however there are a number of side effects. There is a paucity of information regarding long-term use of these medications...
August 22, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28829202/effect-of-heat-moisture-exchanger-on-aerosol-drug-delivery-and-airway-resistance-in-simulated-ventilator-dependent-adults-using-jet-and-mesh-nebulizers
#8
Arzu Ari, Truong Dang, Fahad H Al Enazi, Mohammed M Alqahtani, Abdulrahman Alkhathami, Rowaida Qoutah, Ahmad S Almamary, James B Fink
BACKGROUND: Placement of a heat moisture exchanger (HME) between aerosol generator and patient has been associated with greatly reduced drug delivery. The purpose of this study was to evaluate the effect of filtered and nonfiltered HMEs placed between nebulizer and patient on aerosol deposition and airway resistance (Raw) in simulated ventilator-dependent adults. METHODS: An in vitro lung model was developed to simulate a mechanically ventilated adult (Vt 500 mL, RR 15/min, and PEEP 5 cmH2O, using two inspiratory flow rates 40 and 50 L/min) using an intubated adult manikin with an endotracheal tube (8 mmID)...
August 22, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28828982/development-of-benzimidazole-derivatives-as-novel-anti-platelet-drugs
#9
Wei-Cheng Yao, Lan-Ting Yuan, Wen-Bin Yang, Chih-Hsuan Hsia, Li-Ting Huang, Tzu-Yin Lee, Joen-Rong Sheu, Wan-Jung Lu, Thanasekaran Jayakumar, Ray-Jade Chen
BACKGROUND: Benzimidazoles are privileged biomolecules which form an integral part of vitamin B12 and have been attracting numerous researchers all over the world to assess their potential therapeutic significance. OBJECTIVES: The comparative in vitro antiplatelet activity of newly synthesized benzimidazole derivatives, M3BIM, C2BIM, and L2BIM in thrombin, adenosine diphosphate (ADP) and epinephrine-induced washed human platelets was investigated. METHODS: Reversed-phase silica gel column chromatography, Aggregometry, Flow cytometry and Immunoblotting were used in this study...
August 20, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28828910/phase-transition-of-a-microemulsion-upon-addition-of-cyclodextrin-applications-in-drug-delivery
#10
Sachin S Thakur, Jared Solloway, Anneloes Stikkelman, Ali Seyfoddin, Ilva D Rupenthal
This study reports on the impact of cyclodextrin addition on the phase behavior of microemulsion systems. Three distinct oil-in-water microemulsions were formulated and subjected to increasing concentrations of various cyclodextrins. The prepared formulations underwent visual, textural and microscopic characterization followed by evaluation of their in vitro drug release and ex vivo tissue retention behavior. Combining microemulsions with cyclodextrins resulted in either phase separation or transition into a liquid crystalline state depending the concentration and type of cyclodextrin utilized...
August 22, 2017: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/28828529/clinical-management-of-nocturnal-enuresis
#11
Eberhard Kuwertz-Bröking, Alexander von Gontard
Nocturnal enuresis (NE) is a common health problem. Approximately 10% of 7-year-old children wet the bed regularly during sleep. Enuresis can be categorized into monosymptomatic (MEN) and nonmonosymptomatic (NMEN) forms. MEN occurs without any other symptoms of bladder dysfunction. NMEN is associated with dysfunction of the lower urinary tract with or without daytime incontinence. The rate of comorbid gastrointestinal, behavioral, and emotional disorders is elevated depending upon the subtype of NE. A careful clinical history is fundamental to the evaluation of enuresis...
August 21, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28828521/recombinant-lactococcus-lactis-expressing-bioactive-exendin-4-to-promote-insulin-secretion-and-beta-cell-proliferation-in-vitro
#12
Zhu Zeng, Rui Yu, Fanglei Zuo, Bo Zhang, Huiqin Ma, Shangwu Chen
In recent years, therapeutic peptides have garnered great interest in the pharmaceutical industry for the treatment of diabetes. Lactic acid bacteria (LAB) are an appealing vehicle for safe and convenient oral delivery of bioactive peptide and protein drugs. Exendin-4 (Exd4) is a glucagon-like protein-1 (GLP-1) receptor agonist that is considered an excellent therapeutic peptide drug for type 2 diabetes due to its longer-lasting bioactivity, resulting from resistance to dipeptidyl peptidase 4. We explored Lactococcus lactis with the nisin-controlled gene expression (NICE) system as an oral delivery system for recombinant (r) Exd4 peptide in situ...
August 21, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28827974/ex-vivo-antispasmodic-activity-of-aqueous-extract-of-flowers-of-muntingia-calabura-linn-on-excised-rabbit-s-jejunum
#13
Kannan Vadivel, Gollapudi Sandeep Kumar, Sitty Manohar Babu
OBJECTIVE: The present study has been undertaken with the main objective of evaluating the aqueous extract of flowers of Muntingia calabura for antispasmodic activity on isolated rabbit's jejunum. MATERIALS AND METHODS: The study was carried out on isolated rabbit's jejunum preparations. The aqueous extract of flowers of M. calabura was applied in different doses by cumulative manner without washing the tissue. Spontaneous contractions abolished by the extract were recorded...
July 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28827674/analyses-in-zebrafish-embryos-reveal-that-nanotoxicity-profiles-are-dependent-on-surface-functionalization-controlled-penetrance-of-biological-membranes
#14
Ilkka Paatero, Eudald Casals, Rasmus Niemi, Ezgi Özliseli, Jessica M Rosenholm, Cecilia Sahlgren
Mesoporous silica nanoparticles (MSNs) are extensively explored as drug delivery systems, but in depth understanding of design-toxicity relationships is still scarce. We used zebrafish (Danio rerio) embryos to study toxicity profiles of differently surface functionalized MSNs. Embryos with the chorion membrane intact, or dechoroniated embryos, were incubated or microinjected with amino (NH2-MSNs), polyethyleneimine (PEI-MSNs), succinic acid (SUCC-MSNs) or polyethyleneglycol (PEG-MSNs) functionalized MSNs. Toxicity was assessed by viability and cardiovascular function...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827665/schisandrin-b-reverses-doxorubicin-resistance-through-inhibiting-p-glycoprotein-and-promoting-proteasome-mediated-degradation-of-survivin
#15
Shengpeng Wang, Anqi Wang, Min Shao, Ligen Lin, Peng Li, Yitao Wang
Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracted from Chinese herbal medicine Schisandrae Chinensis Fructus, could significantly enhance the sensitivity of doxorubicin (DOX)-resistant breast cancer and ovarian cancer cells to DOX. Our results showed that Sch B increased the intracellular accumulation of DOX through inhibiting expression and activity of P-glycoprotein (P-gp)...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827372/monocarboxylate-transporter-mct1-promotes-tumor-metastasis-independently-of-its-activity-as-a-lactate-transporter
#16
Valéry L Payen, Myriam Y Hsu, Kristin S Rädecke, Elisabeth Wyart, Thibaut Vazeille, Caroline Bouzin, Paolo E Porporato, Pierre Sonveaux
Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion and metastasis. While host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small molecule drugs to prevent metastasis...
August 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28827286/anti-cancer-drug-hmba-acts-as-an-adjuvant-during-intracellular-bacterial-infections-by-inducing-type-i-ifn-through-sting
#17
Akshamal Mihiranga Gamage, Kok-Onn Lee, Yunn-Hwen Gan
The anti-proliferative agent hexamethylene bisacetamide (HMBA) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. Recently, HMBA has also been shown to trigger HIV transcription from latently infected cells, via a CDK9/HMBA inducible protein-1 dependent process. However, the effect of HMBA on the immune response has not been explored. We observed that pretreatment of human peripheral blood mononuclear cells with HMBA led to a markedly increased production of IL-12 and IFN-γ, but not of TNF-α, IL-6, and IL-8 upon subsequent infection with Burkholderia pseudomallei and Salmonella enterica HMBA treatment was also associated with better intracellular bacterial control...
August 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28827282/a-novel-image-based-high-throughput-screening-assay-discovers-therapeutic-candidates-for-adult-polyglucosan-body-disease
#18
Leonardo J Solemsky, Netaly Khazanov, Hanoch Senderowitz, Peixiang Wang, Berge A Minassian, Igor M Ferreira, Wyatt W Yue, Alexander Lossos, Miguel Weil, Or Kakhlon
Glycogen storage disorders (GSDs) are caused by excessive accumulation of glycogen. Some GSDs (Adult Polyglucosan Body Disease (APBD), Tarui and Lafora diseases) are caused by intracellular accumulation of insoluble inclusions, called polyglucosan bodies (PB), which are chiefly composed of malconstructed glycogen. We developed an APBD patient skin fibroblast cell-based assay for PB identification, where the bodies are identified as amylase-resistant periodic acid-Schiff's (PAS) stained structures, and quantified...
August 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28827149/studies-on-the-interaction-of-the-histone-demethylase-kdm5b-with-tricarboxylic-acid-cycle-intermediates
#19
Hanna Tarhonskaya, Radoslaw P Nowak, Catrine Johansson, Aleksandra Szykowska, Anthony Tumber, Rebecca L Hancock, Pauline Lang, Emily Flashman, Udo Oppermann, Christopher J Schofield, Akane Kawamura
Methylation of lysine-4 of histone H3 (H3K4men) is an important regulatory factor in eukaryotic transcription. Removal of the transcriptionally activating H3K4 methylation is catalysed by histone demethylases, including the JmjC KDM5 subfamily. The JmjC KDMs are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases, some of which are associated with cancer. Altered levels of TCA cycle intermediates, and the associated metabolites D- and L-2-hydroxyglutarate (2HG), can cause changes in chromatin methylation status...
August 18, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28827047/high-drinking-in-the-dark-hdid-mice-are-sensitive-to-the-effects-of-some-clinically-relevant-drugs-to-reduce-binge-like-drinking
#20
John C Crabbe, Angela R Ozburn, Pamela Metten, Amanda Barkley-Levenson, Jason P Schlumbohm, Stephanie E Spence, Wyatt R Hack, Lawrence C Huang
BACKGROUND: There is a serious public health need for better understanding of alcohol use disorder disease mechanisms and for improved treatments. At this writing, only three drugs are approved by the Food and Drug Administration as medications to treat alcohol use disorders - disulfiram, naltrexone, and acamprosate. Binge drinking is a form of abusive alcohol drinking defined by the NIAAA as a drinking to blood alcohol levels (BALs)>0.08% during a period of approximately 2h. To model genetic risk for binge-like drinking, we have used selective breeding to create a unique animal model, High Drinking in the Dark (HDID) mice...
August 4, 2017: Pharmacology, Biochemistry, and Behavior
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