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https://www.readbyqxmd.com/read/28217259/phase-3-trial-of-first-generation-protease-inhibitor-therapy-for-hepatitis-c-virus-human-immunodeficiency-virus-coinfection
#1
Kenneth E Sherman, Minhee Kang, Richard Sterling, Triin Umbleja, Kristen Marks, Jennifer J Kiser, Beverly Alston-Smith, Wayne Greaves, Adeel A Butt, The Actg Birth Study Team
AIM: To evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODS: A prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28217012/-68-ga-prostate-specific-membrane-antigen-positron-emission-tomography-computed-tomography-for-prostate-cancer-imaging-a-narrative-literature-review
#2
REVIEW
Jose M Oliveira, Catarina Gomes, Diogo B Faria, Tiago S Vieira, Fernando A Silva, Joana Vale, Francisco L Pimentel
The (68)Ga-prostate-specific membrane antigen ( (68)Ga-PSMA) has been recently developed to be used, as a ligand, in positron emission tomography/computed tomography (PET/CT) prostate cancer imaging, to detect prostate disease. The main objective of this review was to collect data and findings from other studies and articles to assess, theoretically, if (68)GA-PSMA PET/CT is a more appropriate prostate cancer diagnostic technique in comparison with others available such as CT, (18)F-fluoro-2-deoxyglucose PET/CT, or (18)F-fluoromethylcholine ( (18)F-choline) PET/CT...
January 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28216244/safety-and-efficacy-of-pfspz-vaccine-against-plasmodium-falciparum-via-direct-venous-inoculation-in-healthy-malaria-exposed-adults-in-mali-a-randomised-double-blind-phase-1-trial
#3
Mahamadou S Sissoko, Sara A Healy, Abdoulaye Katile, Freda Omaswa, Irfan Zaidi, Erin E Gabriel, Bourama Kamate, Yacouba Samake, Merepen A Guindo, Amagana Dolo, Amadou Niangaly, Karamoko Niaré, Amatigue Zeguime, Kourane Sissoko, Hama Diallo, Ismaila Thera, Kelly Ding, Michael P Fay, Elise M O'Connell, Thomas B Nutman, Sharon Wong-Madden, Tooba Murshedkar, Adam J Ruben, Minglin Li, Yonas Abebe, Anita Manoj, Anusha Gunasekera, Sumana Chakravarty, B Kim Lee Sim, Peter F Billingsley, Eric R James, Michael Walther, Thomas L Richie, Stephen L Hoffman, Ogobara Doumbo, Patrick E Duffy
BACKGROUND: Plasmodium falciparum sporozite (PfSPZ) Vaccine is a metabolically active, non-replicating, whole malaria sporozoite vaccine that has been reported to be safe and protective against P falciparum controlled human malaria infection in malaria-naive individuals. We aimed to assess the safety and protective efficacy of PfSPZ Vaccine against naturally acquired P falciparum in malaria-experienced adults in Mali. METHODS: After an open-label dose-escalation study in a pilot safety cohort, we did a double-blind, randomised, placebo-controlled trial based in Donéguébougou and surrounding villages in Mali...
February 16, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28213743/development-of-cer-001-preclinical-dose-selection-through-to-phase-i-clinical-findings
#4
Constance H Keyserling, Ronald Barbaras, Renee Benghozi, Jean-Louis Dasseux
BACKGROUND: CER-001 comprises recombinant human apolipoprotein A-I complexed with phospholipids that mimics natural, nascent, pre-β high-density lipoprotein (HDL). We present animal model data showing dose-dependent increases in cholesterol efflux with CER-001 and its subsequent elimination by reverse lipid transport, together with inhibition of atherosclerotic plaque progression. We report the first phase I study results with CER-001 in humans, starting at 0.25 mg/kg, which is 1/80th of the safe dose (20 mg/kg) established in 4-week multiple-dose animal studies dosed every second day...
February 17, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28213249/on-line-flow-injection-molecularly-imprinted-solid-phase-extraction-for-the-preconcentration-and-determination-of-1-hydroxypyrene-in-urine-samples
#5
Montserrat Serrano, Mónica Bartolomé, Juan Carlos Bravo, Gema Paniagua, Judith Gañan, Alejandrina Gallego-Picó, Rosa María Garcinuño
New analytical strategies tend to automation of sample pre-treatment and flow analysis techniques provided a number of enhanced analytical methods allowing high throughput. Flow techniques are usually faster, more robust and more flexible than their batch equivalents. In addition, flow methods use less sample and reagent amounts and reduce analytical costs and waste. A flow injection solid-phase extraction pre-concentration system using a molecularly imprinted polymer (MIP) packed micro-column was developed for the determination of 1-hydroxypyrene in human urine with fluorescence detection...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28211169/a-first-in-human-study-of-ds-1040-an-inhibitor-of-the-activated-form-of-thrombin-activatable-fibrinolysis-inhibitor-in-healthy-subjects
#6
Jin Zhou, Jarema Kochan, Ophelia Yin, Vance Warren, Cynthia Zamora, George Atiee, Joseph Pav, Yasushi Orihashi, Vijay Vashi, Victor Dishy
BACKGROUND: Current treatments for acute ischemic stroke and venous thromboembolism, such as recombinant tissue plasminogen activator and thrombectomy, are limited by a narrow time window and the risk of bleeding. DS-1040 is a novel low-molecular weight compound inhibiting the activated form of thrombin-activatable fibrinolysis inhibitor (TAFIa), developed as a fibrinolysis enhancer for treatment of thromboembolic diseases. OBJECTIVES: This first-in-human, randomized, placebo-controlled, three-part, phase 1 study was conducted to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DS-1040 in healthy subjects...
February 17, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28209906/first-evaluation-of-pet-based-human-biodistribution-and-dosimetry-of-18-f-faza-a-tracer-for-imaging-tumor-hypoxia
#7
Savi Annarita, Elena Incerti, Federico Fallanca, Valentino Bettinardi, Francesca Rossetti, Cristina Monterisi, Antonia Compierchio, Giampiero Negri, Piero Zannini, Luigi Gianolli, Maria Picchio
Fluorine-18 labelled fluoroazomycinarabinoside ((18)F-FAZA) is a positron emission tomography (PET) biomarker for non-invasive identification of regional tumor hypoxia. Aim of the present Phase I study was to firstly evaluate in non-small cell lung cancer patients the human biodistribution and dosimetry of (18)F-FAZA. Methods: Five patients awaiting surgical resection after histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled for the study. The patients underwent a PET/computed tomography (CT) study after the injection of 371±32 MBq of (18)F-FAZA...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209559/irreversible-electroporation-for-the-ablation-of-renal-cell-carcinoma-a-prospective-human-in-vivo-study-protocol-ideal-phase-2b
#8
Mara Buijs, Krijn P van Lienden, Peter Gk Wagstaff, Matthijs Jv Scheltema, Daniel M de Bruin, Patricia J Zondervan, Otto M van Delden, Ton G van Leeuwen, Jean Jmch de la Rosette, M Pilar Laguna
BACKGROUND: Irreversible electroporation (IRE) is an emerging technique delivering electrical pulses to ablate tissue, with the theoretical advantage to overcome the main shortcomings of conventional thermal ablation. Recent short-term research showed that IRE for the ablation of renal masses is a safe and feasible treatment option. In an ablate and resect design, histopathological analysis 4 weeks after radical nephrectomy demonstrated that IRE-targeted renal tumors were completely covered by ablation zone...
February 16, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28203151/cerebellar-tdcs-effects-on-conditioned-eyeblinks-using-different-electrode-placements-and-stimulation-protocols
#9
Linda Beyer, Giorgi Batsikadze, Dagmar Timmann, Marcus Gerwig
There is good evidence that the human cerebellum is involved in the acquisition and timing of classically conditioned eyeblink responses (CRs). Animal studies suggest that the cerebellum is also important in CR extinction and savings. Cerebellar transcranial direct current stimulation (tDCS) was reported to modulate CR acquisition and timing in a polarity dependent manner. To extent previous findings three experiments were conducted using standard delay eyeblink conditioning. In a between-group design, effects of tDCS were assessed with stimulation over the right cerebellar hemisphere ipsilaterally to the unconditioned stimulus (US)...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28195199/pemafibrate-a-novel-selective-peroxisome-proliferator-activated-receptor-alpha-modulator-improves-the-pathogenesis-in-a-rodent-model-of-nonalcoholic-steatohepatitis
#10
Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Kento Imajo, Koji Fujita, Masato Yoneda, Toshiaki Takizawa, Satoru Saito, Yoji Nagashima, Atsushi Nakajima
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193657/preclinical-pharmacokinetics-and-first-in-human-pharmacokinetics-safety-and-tolerability-of-velpatasvir-a-pangenotypic-hcv-ns5a-inhibitor-in-healthy-subjects
#11
Erik Mogalian, Polina German, Brian P Kearney, Cheng Yong Yang, Diana Brainard, John Link, John McNally, LingLing Han, John Ling, Anita Mathias
Preclinical characterization of velpatasvir (VEL; GS-5816), an inhibitor of HCV NS5A protein, demonstrated favourable in vitro and in vivo properties, including potent antiviral activity against hepatitis C virus genotypes 1 to 6 replicon, good metabolic stability, low systemic clearance, and adequate bioavailability and physicochemical properties to warrant clinical evaluation. The Phase 1 (first-in-human) study evaluated the safety, tolerability, and pharmacokinetics of VEL in healthy human subjects following administration of single and multiple (7) once-daily ascending doses and of VEL in the presence and absence of food...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28192438/advances-in-neglected-tropical-disease-vaccines-developing-relative-potency-and-functional-assays-for-the-na-gst-1-alhydrogel-hookworm-vaccine
#12
Jill B Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J Hotez, David Diemert, Jeffrey M Bethony
A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are not relevant for this investigational product...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28191763/electrical-cell-substrate-impedance-spectroscopy-can-monitor-age-grouped-human-adipose-stem-cell-variability-during-osteogenic-differentiation
#13
Rachel C Nordberg, Jianlei Zhang, Emily H Griffith, Matthew W Frank, Binil Starly, Elizabeth G Loboa
Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell-substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188809/preventing-relapse-after-incentivized-choice-treatment-a-laboratory-model
#14
REVIEW
Mark E Bouton, Eric A Thrailkill, Cecilia L Bergeria, Danielle R Davis
Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1...
February 7, 2017: Behavioural Processes
https://www.readbyqxmd.com/read/28187915/effect-of-ileal-bile-acid-transporter-inhibitor-gsk2330672-on-pruritus-in-primary-biliary-cholangitis-a-double-blind-randomised-placebo-controlled-crossover-phase-2a-study
#15
Vinod S Hegade, Stuart F W Kendrick, Robert L Dobbins, Sam R Miller, Douglas Thompson, Duncan Richards, James Storey, George E Dukes, Margaret Corrigan, Ronald P J Oude Elferink, Ulrich Beuers, Gideon M Hirschfield, David E Jones
BACKGROUND: Up to 70% of patients with primary biliary cholangitis develop pruritus (itch) during the course of their disease. Treatment of pruritus in primary biliary cholangitis is challenging and novel therapies are needed. Ursodeoxycholic acid, the standard first-line treatment for primary biliary cholangitis, is largely ineffective for pruritus. We investigated the efficacy and safety of GSK2330672, a selective inhibitor of human ileal bile acid transporter (IBAT), in patients with primary biliary cholangitis with pruritus...
February 7, 2017: Lancet
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#16
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28181614/the-first-examples-of-multiply-bonded-dirhenium-iii-ii-paramagnetic-complexes-containing-nitrobenzoate-ligands-spectroscopic-structural-cytotoxicity-and-computational-studies
#17
Suman Mallick, Mrinal Kanti Ghosh, Suman Mandal, Vinayak Rane, Ramakant Kadam, Annesha Chatterjee, Arindam Bhattacharyya, Swarup Chattopadhyay
4-Nitrobenzoic acid, 3-nitrobenzoic acid and 4'-nitro[1,1'-biphenyl]-4-carboxylic acid react with the multiply bonded paramagnetic dirhenium(iii,ii) complex Re2(μ-O2CCH3)Cl4(μ-Ph2PCH2PPh2)2 (1) in refluxing ethanol to afford the paramagnetic substitution products of the type Re2(μ-L)Cl4(μ-Ph2PCH2PPh2)2, where L represents the nitrobenzoate ligands [L = 4-nitrobenzoate, 2; 3-nitrobenzoate, 3; 4'-nitro[1,1'-biphenyl]-4-carboxylate, 4]. These are the first examples of paramagnetic dirhenium complexes containing nitrobenzoate ligands...
February 9, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28181260/a-mechanism-based-pharmacokinetic-pharmacodynamic-model-for-bococizumab-a-humanized-monoclonal-antibody-against-proprotein-convertase-subtilisin-kexin-type-9-and-its-application-in-early-clinical-development
#18
Chandrasekhar Udata, Pamela D Garzone, Barry Gumbiner, Tenshang Joh, Hong Liang, Kai-Hsin Liao, Jason H Williams, Xu Meng
Bococizumab (RN316/PF-04950615), a humanized monoclonal antibody, binds to secreted proprotein convertase subtilisin/kexin type 9 (PCSK9) and prevents its downregulation of low-density lipoprotein receptor, leading to improved clearance and reduction of low-density lipoprotein cholesterol (LDL-C) in plasma. A mechanism-based drug-target binding model was developed, accounting for bococizumab, PCSK9, and LDL-C concentrations and the effects of concomitant administration of statins. This model was utilized to better understand the pharmacokinetic/pharmacodynamic (PK/PD) data obtained from 3 phase 1 and 2 phase 2a clinical studies...
February 9, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28163135/a-mechanism-based-pharmacokinetic-enzyme-turnover-model-for-dichloroacetic-acid-auto-inhibition-in-rats
#19
Yu Jiang, Gary Milavetz, Margaret O James, Guohua An
Dichloroacetic acid (DCA), a halogenated organic acid, is a pyruvate dehydrogenase kinase (PDK) inhibitor that has been used to treat congenital or acquired lactic acidosis and is currently in early phase clinical trials for cancer treatment. DCA was found to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta 1 (GSTZ1-1), resulting in non-linear kinetics and abnormally high accumulation ratio after repeated dosing. In this analysis, a semi-mechanistic pharmacokinetic-enzyme turn over model was developed for the first time to capture DCA auto-inhibition, gastrointestinal region-dependent absorption, and time dependent change in bioavailability in rats...
February 2, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28161451/feasibility-of-laser-marking-in-barrett-s-esophagus-with-volumetric-laser-endomicroscopy-first-in-man-pilot-study
#20
A Swager, A J de Groof, S L Meijer, B L Weusten, W L Curvers, J J Bergman
BACKGROUND AND AIM: Volumetric laser endomicroscopy (VLE) provides a circumferential scan of the esophageal wall layers, and has potential to improve neoplasia detection in Barrett's esophagus (BE). The novel VLE laser marking system enables direct in vivo marking of suspicious areas as identified on VLE. These laser marked areas can subsequently be targeted for biopsies. The aim was to evaluate the visibility and positional accuracy of laser marks in different esophageal tissue types on white-light endoscopy (WLE) and VLE...
February 1, 2017: Gastrointestinal Endoscopy
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