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https://www.readbyqxmd.com/read/29350320/ethical-implications-in-vaccine-pharmacotherapy-for-treatment-and-prevention-of-drug-of-abuse-dependence
#1
Anna Carfora, Paola Cassandro, Alessandro Feola, Francesco La Sala, Raffaella Petrella, Renata Borriello
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway...
January 19, 2018: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/29346071/identification-of-potential-inhibitors-against-nuclear-dam1-complex-subunit-ask1-of-candida-albicans-using-virtual-screening-and-md-simulations
#2
Himanshu Tripathi, Feroz Khan
Identification of hit compounds against specific target form the starting point for a drug discovery program. A consistent decline of new chemical entities (NCEs) in recent years prompted a challenge to explore newer approaches to discover potential hit compounds that in turn can be converted into leads, and ultimately drug with desired therapeutic efficacy. The vast amount of omics and activity data available in public databases offers an opportunity to identify novel targets and their potential inhibitors...
January 1, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29345117/candida-auris-a-systematic-review-and-meta-analysis-of-current-updates-on-an-emerging-multidrug-resistant-pathogen
#3
John Osei Sekyere
From 2009, Candida auris has emerged as a multidrug-resistant ascomycete yeast pathogen with the capacity for easy transmission between patients and hospitals, as well as persistence on environmental surfaces. Its association with high mortalities, breakthrough and persistent candidaemia, inconsistencies in susceptibility testing results, misidentification by available commercial identification systems and treatment failure, complicates its management and detection. Within the last nine years, C. auris has been increasingly reported from far-Eastern Asia, the Middle East, Africa, Europe, South and North America with substantial fatalities and misidentification...
January 18, 2018: MicrobiologyOpen
https://www.readbyqxmd.com/read/29344898/methods-for-high-throughput-drug-combination-screening-and-synergy-scoring
#4
Liye He, Evgeny Kulesskiy, Jani Saarela, Laura Turunen, Krister Wennerberg, Tero Aittokallio, Jing Tang
Gene products or pathways that are aberrantly activated in cancer but not in normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials but so far showed limited efficacy mostly due to variability in treatment responses and often rapidly emerging resistance. Toward more effective treatment options, we will need multi-targeted drugs or drug combinations, which selectively inhibit the viability and growth of cancer cells and block distinct escape mechanisms for the cells to become resistant...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29342289/recent-advances-in-kidney-transplantation-a-viewpoint-from-the-descartes-advisory-board
#5
Daniel Abramowicz, Rainer Oberbauer, Uwe Heemann, Ondrej Viklicky, Licia Peruzzi, Christophe Mariat, Marta Crespo, Klemens Budde, Gabriel C Oniscu
Transplantation medicine is a rapidly evolving field. Keeping afloat of the published literature to offer the best clinical care to our patients is a daunting task. As part of its educational mission, the Descartes advisory board identified seven topics in kidney transplantation where there has been substantial progresses over the last years: kidney allocation within Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies; the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new immunosuppressive drugs in the pipeline; strategies for immunosuppression minimization; and the continuous enigma of focal segmental glomerular sclerosis recurrence after transplantation...
January 12, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29341478/translational-systems-pharmacology-based-predictive-assessment-of-drug-induced-cardiomyopathy
#6
Dimitris E Messinis, Ioannis N Melas, Junguk Hur, Navya Varshney, Leonidas G Alexopoulos, Jane P F Bai
Drug-induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug's signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs' signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0...
January 17, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29341142/evolutionary-and-genetic-features-of-drug-targets
#7
REVIEW
Yuan Quan, Zhong-Yi Wang, Xin-Yi Chu, Hong-Yu Zhang
In the modern drug discovery pipeline, identification of novel drug targets is a critical step. Despite rapid progress in developing biomedical techniques, it is still a great challenge to find promising new targets from the ample space of human genes. This fact is partially responsible for the situation of "more investments, fewer drugs" in the pharmaceutical industry. A series of recent researches revealed that successfully targeted genes share some common evolutionary and genetic features, which means that the knowledge accumulated in modern evolutionary biology and genetics is very helpful to identify potential drug targets and to find new drugs as well...
January 17, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29336981/challenges-and-opportunities-for-the-subcutaneous-delivery-of-therapeutic-proteins
#8
REVIEW
Michael R Turner, Sathy V Balu-Iyer
Biotherapeutics are a rapidly growing drug class and well over 200 biotherapeutics have already obtained approval, with about fifty of these being approved in 2015 and 2016 alone 1. Several hundred protein therapeutic products are still in the pipeline, including interesting new approaches to treatment. Due to patients' convenience of at home administration and reduced number of hospital visits as well as the reduction in treatment costs, subcutaneous (SC) administration of biologics is of increasing interest...
January 11, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29336544/identification-of-collateral-sensitivity-to-dihydroorotate-dehydrogenase-inhibitors-in-i-plasmodium-falciparum-i
#9
Leila Saxby Ross, Maria Jose Lafuente-Monasterio, Tomoyo Sakata-Kato, Rebecca E K Mandt, Francisco-Javier Gamo, Dyann F Wirth, Amanda K Lukens
Drug resistance has been reported for every antimalarial in use highlighting the need for new strategies to protect the efficacy of therapeutics in development. We have previously shown that resistance can be suppressed with a population biology trap: by identifying situations where resistance to one compound confers hypersensitivity to another (collateral sensitivity), we can design combination therapies that not only kill the parasite, but also guide its evolution away from resistance. We applied this concept to the Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme, a well validated antimalarial target with inhibitors in the development pipeline...
January 16, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29336263/in-vitro-methods-for-in-vitro-in-vivo-correlation-ivivc-for-poorly-water-soluble-drugs-lipid-based-formulation-perspective
#10
Mohsin Kazi, Rayan Rayan Al Amri, Fars K Alanazi, Muhammad Delwar Hussain
A great number of new drug candidates identified from the discovery pipeline are poorly water soluble, which is a drawback to bring such candidates into the pharmaceutical market. Formulating these compounds as self-emulsifying/microemulsifying/ nanoemulsifying drug delivery systems (SEDDS/SMEDDS/SNEDDS) within lipid based formulations is of growing interests. Some of the recent studies have resulted in commercial products that provided improved bioavailability and dissolution due to the better dispersion properties of SEDDS/SMEDDS/SNEDDS...
January 15, 2018: Current Drug Delivery
https://www.readbyqxmd.com/read/29332642/current-affairs-future-perspectives-of-tuberculosis-and-antitubercular-agents
#11
REVIEW
Jineetkumar Gawad, Chandrakant Bonde
Tuberculosis (TB) is the major threat for humans from past several decades. Even after advent of several antitubercular drugs, researchers are still struggling for the mycobacterial infections in humans are TB and leprosy. Chronic infections caused by Mycobacterium tuberculosis and Mycobacterium leprae. A particular problem with both of these organisms is that they can survive inside macrophages after phagocytosis, unless these cells are activated by cytokines produced by T-lymphocytes, because of this researchers are not yet succeeded in finding effective treatment on TB...
January 2018: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/29323575/phase-ii-investigational-oral-drugs-for-the-treatment-of-radio-chemotherapy-induced-oral-mucositis
#12
Stephen T Sonis, Alessandro Villa
Oral mucositis is a significant unmet clinical need for many cancer patients. The biological complexity of mucositis' pathogenesis provides a number of mechanistic targets suitable as pharmacologic targets. The diversity of targets has stimulated drug development in search of an effective intervention. In this paper, we review a range of agents that are currently being evaluated. Areas covered: Drugs for management of oral mucositis vary in formulation, route of administration and biological target. Most propose to interrupt the initiation of injury by suppressing activation of the innate immune response or countering oxidative stress, or minimizing downstream inflammatory responses...
January 11, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29322595/identification-of-new-%C3%AE-synuclein-regulator-by-nontraditional-drug-development-pipeline
#13
Xi Chen, Sonja W Scholz
No abstract text is available yet for this article.
January 11, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29320765/emerging-treatment-options-in-atopic-dermatitis-systemic-therapies
#14
Uffe Nygaard, Christian Vestergaard, Mette Deleuran
The pathogenesis of atopic dermatitis (AD) is multifactorial and intricate, and the clinical presentation of the condition varies greatly. Symptoms and severity depend on individual trigger factors and stage of the disease. The majority of AD patients are sufficiently treated with emollients in combination with existing topical or systemic therapies. Yet treatment failure with existing drugs and treatment options can be a significant clinical problem. New treatments are under development, and the majority of these new drugs focus on targeting a skewed immune response in AD...
January 11, 2018: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/29320160/efforts-aimed-to-reduce-attrition-in-antimalarial-drug-discovery-a-systematic-evaluation-of-current-antimalarial-targets-portfolio
#15
María Jesus Chaparro, Felix Calderon, Pablo Castañeda, Elena Fernandez Alvaro, Raquel Gabarro, Francisco-Javier Gamo, María G Gómez-Lorenzo, Julio Martín, Esther Fernandez
Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits...
January 10, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29315487/using-extensional-flow-to-reveal-diverse-aggregation-landscapes-for-three-igg1-molecules
#16
Leon F Willis, Amit Kumar, John Dobson, Nick Bond, David Lowe, Richard Turner, Sheena E Radford, Nikil Kapur, David J Brockwell
Monoclonal antibodies (mAbs) currently dominate the biopharmaceutical sector due to their potency and efficacy against a range of disease targets. These proteinaceous therapeutics are, however, susceptible to unfolding, mis-folding and aggregation by environmental perturbations. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation and storage. Hydrodynamic forces have also been linked to aggregation, but the ability of different flow fields (e.g. shear and extensional flow) to trigger aggregation has remained unclear...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29315477/enrichment-of-high-affinity-subclasses-and-glycoforms-from-serum-derived-igg-using-fc%C3%AE-rs-as-affinity-ligands
#17
Boesch Aw, Kappel Jh, Mahan Ae, Chu Th, Crowley Ar, Osei-Owusu Ny, Alter G, Ackerman Me
As antibodies continue to gain predominance in drug discovery and development pipelines, efforts to control and optimize their activity in vivo have matured to incorporate sophisticated abilities to manipulate engagement of specific Fc binding partners. Such efforts to promote diverse functional outcomes include modulating IgG-Fc affinity for FcγRs to alternatively potentiate or reduce effector functions, such as antibody-dependent cellular cytotoxicity and phagocytosis. While a number of natural and engineered Fc features capable of eliciting variable effector functions have been demonstrated in vitro and in vivo, elucidation of these important functional relationships has taken significant effort through use of diverse genetic, cellular and enzymatic techniques...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29307065/metals-in-bones-of-the-middle-aged-inhabitants-of-sardinia-island-italy-to-assess-nutrition-and-environmental-exposure
#18
Beatrice Bocca, Giovanni Forte, Valentina Giuffra, Rita Maria Serra, Yolande Asara, Cristiano Farace, Marco Milanese, Eugenia Tognotti, Andrea Montella, Pasquale Bandiera, Roberto Madeddu
Metals in bones of 72 subjects lived between the twelfth and eighteenth century AC and collected in four Sardinian (Italian insular region) burial sites (Alghero, Bisarcio, Geridu, and Sassari) were determined and used as biomarkers to evaluate diet and potential social-environmental differences. Concentrations of Ba, Ca, Cd, Cu, Hg, Pb, Sr, and Zn were quantified in different types of compact bone (femur, fibula, humerus, radius, tibia, ulna) by sector field inductively coupled plasma mass spectrometry previous acidic digestion and differences among the various burial sites, centuries, types of bone, gender, and age were explored by univariate and multivariate analyses...
January 6, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29303083/patented-and-approval-scenario-of-nanopharmaceuticals-with-relevancy-to-biomedical-application-manufacturing-procedure-and-safety-aspects
#19
Vijay Agarwal, Meenakshi Bajpai, Ashish Sharma
A term 'nanopharmaceuticals' give the emphasis on the discovery, development and delivery of the drugs to the specific site using different delivery systems. Nanopharmaceutical field is a thrust area in which the development is going on progressively but the many new challenges are also arises continuously, such as regulatory requirements, identification of therapeutic targets, cost-effective and efficient tools for delivering the drug, standardization of different characterization method, etc. Some products related to this area that can be consistently and reproducibly prepared with a desired quality and is safe for the public, has been approved by the different regulatory agencies...
January 4, 2018: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29298811/sources-and-biological-activities-of-marine-sulfated-steroids
#20
Francisca Carvalhal, Marta Correia-da-Silva, Maria Emília Sousa, Madalena Pinto, Anake Kijjoa
Marine environment is rich in structurally unique molecules and can be an inspiring source of novel drugs. Currently, six marine-derived drugs are in the market with FDA approval and several more are in the clinical pipeline. Structurally-diverse and complex secondary metabolites have been isolated from the marine world and these include sulfated steroids. Biological activities of nearly 150 marine sulfated steroids reported from 1978 to 2017 are compiled and described, namely antimicrobial, antitumor, cardiovascular, and antifouling activities...
January 3, 2018: Journal of Molecular Endocrinology
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