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https://www.readbyqxmd.com/read/28650053/in-situ-crystal-growth-of-gold-nanocrystals-on-upconversion-nanoparticles-for-synergistic-chemo-photothermal-therapy
#1
Ruoyan Wei, Wensong Xi, Haifang Wang, Jinliang Liu, Torsten Mayr, Liyi Shi, Lining Sun
A multifunctional cancer therapy nanocomposite was proposed and synthesized by linking the pH-responsive SH-PEG-DOX prodrug onto gold nanocrystals that were grown in situ on the surface of upconversion nanoparticles (UCNPs). In the structure of the SH-PEG-DOX prodrug, a hydrazone bond was utilized for subsequent pH-responsive drug release in the intracellular acidic microenvironment of cancer cells. This innovative assembly method is facile and mild, and can be used to obtain nanocomposites of UCNPs and gold, which show excellent photostability and biocompatibility...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649690/enzymatic-conjugation-using-branched-linkers-for-constructing-homogeneous-antibody-drug-conjugates-with-high-potency
#2
Yasuaki Anami, Wei Xiong, Xun Gui, Mi Deng, Cheng Cheng Zhang, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama
Antibody-drug conjugates (ADCs) are emerging therapeutic agents in the treatment of cancer, and various conjugation strategies and chemical linkers have been developed to efficiently construct ADCs. Despite previous extensive efforts for improving conjugation efficiency and ADC homogeneity, most ADC linkers developed to date load only single payloads. Branched linkers that can load multiple payload molecules have yet to be fully explored. It is logical to envisage that a multi-loading strategy allows for increase in drug-to-antibody ratio (DAR) with less chemical or enzymatic modification to the antibody structure compared to traditional linear linkers, leading to efficient ADC construction, minimal destabilization of the antibody structure, and enhanced ADC efficacy...
June 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28646446/innovations-in-the-endovascular-management-of-critical-limb-ischemia-retrograde-tibiopedal-access-and-advanced-percutaneous-techniques
#3
REVIEW
Jihad A Mustapha, Larry J Diaz-Sandoval, Fadi Saab
PURPOSE OF REVIEW: Retrograde tibiopedal access and interventions have contributed to advance of endovascular techniques to treat critical limb ischemia (CLI) patients. This review encompasses the spectrum from advanced diagnostic imaging and technical therapeutic approaches for infrapopliteal occlusions, to a discussion of current standards and future directions. RECENT FINDINGS: Contemporary studies of infrapopliteal angioplasty show suboptimal short-term and 1-year clinical outcomes...
August 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28646080/considerations-from-the-iq-induction-working-group-in-response-to-drug-drug-interaction-guidances-from-regulatory-agencies-focus-on-down-regulation-cyp2c-induction-and-cyp2b6-positive-control
#4
Niresh Hariparsad, Diane Ramsden, Jairam Palamanda, Joshua G Dekeyser, Odette A Fahmi, Jane R Kenny, Heidi Einolf, Michael Mohutsky, Magalie Pardon, Amy Y Siu, Liangfu Chen, Michael Sinz, Barry Jones, Robert Walsky, Shannon Dallas, Suresh K Balani, George Zhang, David Buckley, Donald Tweedie
The European Medicines Agency (EMA), the Pharmaceutical and Medical Devices Agency and the Food and Drug Administration have issued guidances for the conduct of drug-drug interaction (DDI) studies. To examine the applicability of these regulatory recommendations specifically for induction, a group of scientists, under the auspices of the Drug Metabolism Leadership Group of the Innovation and Quality (IQ) Consortium, formed the Induction Working Group (WG). A team of 20 scientists, from 16 of the 39 pharmaceutical companies, which are members of the IQ Consortium, and three Contract Research Organizations, reviewed the recommendations, focusing initially on the current EMA guidance...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28645529/nanoparticle-based-dressing-the-future-of-wound-treatment
#5
REVIEW
Morgane Berthet, Yves Gauthier, Céline Lacroix, Bernard Verrier, Claire Monge
Reconstructing functional skin after a wound remains a challenge due to the complexity of healing. In this regard, biocompatible nanoparticles (NPs) carrying and releasing bioactive drugs in a controlled and sustained manner may significantly improve the efficacy of wound therapies compared with current treatments. Topical administration of drug-loaded NPs allows optimal delivery to the dermis and improves product efficacy. Furthermore, associating NPs with scaffolds represents a new concept of 'dressing'. Experimental in vivo, ex vivo, and in vitro models have been developed in preclinical assays to evaluate the beneficial effects of nanoparticulate dressings...
June 20, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28643861/challenges-in-the-development-of-novel-cardiovascular-therapies
#6
T J Hwang, A S Kesselheim
Cardiovascular disease accounts for nearly one in three deaths globally, but few novel therapies have reached patients and clinicians in recent years. This translational report reviews trends in the development and approval of cardiovascular drugs and evaluates recent innovation in the field of cardiovascular disease therapeutics. New policies are needed to better support the development of safe and effective therapies with the greatest potential to improve patient health outcomes.
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28643779/drugging-the-undruggable-cancer-targets
#7
REVIEW
Chi V Dang, E Premkumar Reddy, Kevan M Shokat, Laura Soucek
The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies...
June 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28641333/validation-of-brain-angiotensin-system-blockade-as-a-novel-drug-target-in-pharmacological-treatment-of-neuropsychiatric-disorders
#8
Dominik Wincewicz, Jan J Braszko
Retreat in psychiatric drug development results in innovative medication decline that might be at least partially overcome by adjunct therapy. New evidence from clinical studies has shown a possible role for brain Renin-Angiotensin System (RAS) in both affective and psychotic disorders. Simultaneously, rapidly accumulating data from basic studies indicate effectiveness of central RAS blockade in much broader range of neuropsychiatric disease. Recent findings implicate brain RAS, especially Angiotensin II (Ang II), in neural pathophysiology of mental disorders through neuroendocrine modulation and effects on neurotransmitter release, mostly noradrenaline, acetylcholine and dopamine...
June 22, 2017: Pharmacopsychiatry
https://www.readbyqxmd.com/read/28640968/the-impact-of-andean-patagonian-mycoflora-in-the-search-for-new-lead-molecules
#9
REVIEW
Pedro M Aqueveque, Carlos L Cespedes, Isao Kubo, David S Seigler, Olov Sterner
Secondary metabolites from fungi have become a major source of chemical innovation in programs searching for lead molecules with bioactivities, especially over the last 50 years. In this review, we discuss the fundamental considerations in the discovery of molecules for agricultural and medicinal uses. This group of organisms possesses a strong potential for scientific and industrial communities. Recently, the incorporation of new technologies for the artificial cultivation of fungi and the use of better equipment to isolate and identify active metabolites has allowed the discovery of leading molecules for the design of new and safer drugs and pesticides...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28637670/a-randomised-double-blind-trial-to-demonstrate-bioequivalence-of-gp2013-and-reference-rituximab-combined-with-methotrexate-in-patients-with-active-rheumatoid-arthritis
#10
Josef S Smolen, Stanley B Cohen, Hans-Peter Tony, Morton Scheinberg, Alan Kivitz, Andra Balanescu, Juan Gomez-Reino, Liyi Cen, Peijuan Zhu, Tamas Shisha
OBJECTIVES: The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment. METHODS: In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid...
June 21, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28637198/multi-target-activity-of-hemidesmus-indicus-decoction-against-innovative-hiv-1-drug-targets-and-characterization-of-lupeol-mode-of-action
#11
Francesca Esposito, Manuela Mandrone, Claudia Del Vecchio, Ilaria Carli, Simona Distinto, Angela Corona, Mariacaterina Lianza, Dario Piano, Massimo Tacchini, Elias Maccioni, Filippo Cottiglia, Elisa Saccon, Ferruccio Poli, Cristina Parolin, Enzo Tramontano
Despite the availability of several anti-retrovirals there is still an urgent need for developing novel therapeutic strategies and finding new drugs against underexplored HIV-1 targets. Among them, there are the HIV-1 Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) function and the cellular α-glucosidase, involved in the control mechanisms of N-linked glycoproteins formation in the endoplasmic reticulum. It is known that many natural compounds, such as pentacyclic triterpenes, are a promising class of HIV-1 inhibitors...
June 20, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#12
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635521/assessment-of-an-innovative-voluntary-substance-abuse-treatment-program-designed-to-replace-compulsory-drug-detention-centers-in-malaysia
#13
Farrah Khan, Archana Krishnan, Mansur A Ghani, Jeffrey A Wickersham, Jeannia J Fu, Sin How Lim, Sangeeth Kaur Dhaliwal, Adeeba Kamarulzaman, Frederick L Altice
BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services. OBJECTIVES:   We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan...
February 22, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#14
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28633699/migration-histories-of-multidrug-resistant-tuberculosis-patients-from-the-thailand-myanmar-border-2012-2014
#15
S S Thi, D M Parker, L L Swe, S Pukrittayakamee, C L Ling, K Amornpaisarnloet, M Vincenti-Delmas, F H Nosten
SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health threat in South-East Asia. TB is typically a disease of poverty and can be spread by infectious humans who migrate from one region to another. DESIGN: We interviewed 20 MDR-TB patients on the Thailand-Myanmar border with regard to their migration histories. Migration origins and destinations were mapped. RESULTS: All but one participant had a history of migration, and maps of migration ranges revealed wide geographic dispersal...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28631775/-innovations-in-the-treatment-of-ovarian-cancer-analysis-of-the-therapeutic-development-from-platinum-to-immunotherapy
#16
Gesuino Angius, Pierangela Sepe, Anselmo Papa, Silverio Tomao, Federica Tomao
Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease...
June 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28630771/polypharmacy-among-underserved-older-african-american-adults
#17
Mohsen Bazargan, James Smith, Masoud Movassaghi, David Martins, Hamed Yazdanshenas, Seyede Salehe Mortazavi, Gail Orum
The purpose of the present study was to examine correlates of polypharmacy among underserved community-dwelling older African American adults. Methods. This study recruited 400 underserved older African Americans adults living in South Los Angeles. The structured face-to-face interviews collected data on participants' characteristics and elicited data pertaining to the type, frequency, dosage, and indications of all medications used by participants. Results. Seventy-five and thirty percent of participants take at least five and ten medications per day, respectively...
2017: Journal of Aging Research
https://www.readbyqxmd.com/read/28630127/deciphering-function-of-new-gonococcal-vaccine-antigens-using-phenotypic-microarrays
#18
Benjamin I Baarda, Sarah Emerson, Philip J Proteau, Aleksandra E Sikora
The function and extracellular location of cell envelope proteins make them attractive candidates for developing vaccines against bacterial diseases, including challenging, drug-resistant pathogens such as Neisseria gonorrhoeae Proteomics-driven reverse vaccinology delivered multiple gonorrhea vaccine candidates; however, the biological functions of many of them remain to be elucidated. Herein, the functions of six gonorrhea vaccine candidates - NGO2121, NGO1985, NGO2054, NGO2111, NGO1205, and NGO1344 - in cell envelope homeostasis were probed using phenotype microarrays with 1,056 conditions and a ΔbamE mutant (Δngo1780) as a reference of perturbed outer membrane integrity...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28629920/pulmonary-hypertension-in-parenchymal-lung-diseases-any-future-for-new-therapies
#19
REVIEW
Sergio Harari, Davide Elia, Marc Humbert
Pulmonary hypertension (PH) due to chronic lung diseases is associated with a poor prognosis, regardless of the underlying respiratory condition. Updated PH guidelines recommend optimal treatment of the underlying lung disease, including long-term oxygen therapy, in patients with chronic hypoxaemia despite the lack of randomized controlled clinical trials supporting this statement. So far, randomized controlled trials on drugs approved for pulmonary arterial hypertension (PAH) have yielded discouraging results in both interstitial lung diseases (ILD) and chronic obstructive pulmonary diseases (COPD) with PH...
June 16, 2017: Chest
https://www.readbyqxmd.com/read/28629754/improving-compliance-with-surgical-antibiotic-prophylaxis-guidelines-a-multicenter-evaluation
#20
Cristiane Schmitt, Rubia Aparecida Lacerda, Ruth Natalia Teresa Turrini, Maria Clara Padoveze
BACKGROUND: Improving surgical antibiotic prophylaxis (SAP) use is an important element in the control of antimicrobial resistance. However, compliance with SAP guidelines is unsatisfactory. This study investigated the level of compliance with SAP guidelines in neurosurgery, and institutional characteristics associated with compliance. METHODS: This study assessed surgeries in 9 Brazilian hospitals. Medical record reviews and a structured questionnaire were used to assess compliance and to describe institutional characteristics...
June 16, 2017: American Journal of Infection Control
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