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https://www.readbyqxmd.com/read/29791525/2-3-8-trisubstituted-quinolines-with-antimalarial-activity
#1
Pablo D G Martinez, Susann H Krake, Maitia L Poggi, Simon F Campbell, Paul A Willis, Luiz C Dias
Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P...
May 21, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29786558/new-substrates-for-stem-cell-control
#2
REVIEW
Sara Schmidt, Annamaria Lilienkampf, Mark Bradley
The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29785773/molecular-tension-probes-to-investigate-the-mechanopharmacology-of-single-cells-a-step-toward-personalized-mechanomedicine
#3
Kornelia Galior, Victor Pui-Yan Ma, Yang Liu, Hanquan Su, Nusaiba Baker, Reynold A Panettieri, Cherry Wongtrakool, Khalid Salaita
Given that dysregulation of mechanics contributes to diseases ranging from cancer metastasis to lung disease, it is important to develop methods for screening the efficacy of drugs that target cellular forces. Here, nanoparticle-based tension sensors are used to quantify the mechanical response of individual cells upon drug treatment. As a proof-of-concept, the activity of bronchodilators is tested on human airway smooth muscle cells derived from seven donors, four of which are asthmatic. It is revealed that airway smooth muscle cells isolated from asthmatic donors exhibit greater traction forces compared to the control donors...
May 22, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29785534/an-enzyme-free-homogenous-electrochemical-assay-for-sensitive-detection-of-the-plasmid-mediated-colistin-resistance-gene-mcr-1
#4
Bo Li, Zhixin Chai, Xiaohui Yan, Chunchen Liu, Bo Situ, Ye Zhang, Weilun Pan, Shihua Luo, Jianhua Liu, Lei Zheng
Antibiotic resistance associated with the mcr-1 gene of Gram-negative bacteria, which confers resistance to drugs of last resort and has the potential to spread via plasmids, is one of the most pressing issues facing global health today. Point-of-care testing for the mcr-1 gene is needed to aid in the identification of colistin resistance in the field and to control its horizontal transmission. Here, we report the successful development of an enzyme-free homogenous electrochemical strategy for sensitive detection of the antibiotic resistance gene mcr-1 using the hybridization chain reaction and mcr-1-specific toehold probe...
May 22, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29776460/validation-of-the-betastar-%C3%A2-advanced-for-beta-lactams-test-kit-for-the-screening-of-bulk-tank-and-tanker-truck-milks-for-the-presence-of-beta-lactam-drug-residues
#5
Andrew Denhartigh, Lindsay Reynolds, Katherine Palmer, Frank Klein, Jennifer Rice, John J Rejman
A validation study was conducted for an immunochromatographic method (BetaStar® Advanced for Beta-lactams) for the detection of beta-lactam residues in raw, commingled bovine milk. The assay detected amoxicillin, ampicillin, cloxacillin, penicillin, cephapirin, and ceftiofur below the U.S. Food and Drug Administration tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. The results of internal and independent laboratory dose-response studies employing spiked samples were in agreement...
May 18, 2018: Journal of AOAC International
https://www.readbyqxmd.com/read/29776438/uninterrupted-monitoring-of-drug-effects-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-with-bioluminescence-ca-2-microscopy
#6
Kazushi Suzuki, Takahito Onishi, Chieko Nakada, Shunsuke Takei, Matthew J Daniels, Masahiro Nakano, Tomoki Matsuda, Takeharu Nagai
OBJECTIVE: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+ ), and its application in a customized microscope for high-throughput drug screening. RESULTS: GmNL(Ca2+ ) gives a 140% signal change with Ca2+ , and can image drug-induced changes of Ca2+ dynamics in cultured cells...
May 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29769307/orally-bioavailable-and-blood-brain-barrier-penetrating-atm-inhibitor-az32-radiosensitizes-intracranial-gliomas-in-mice
#7
Jeremy Karlin, Jasmine Allen, Syed F Ahmad, Gareth Hughes, Victoria Sheridan, Rajesh Odedra, Paul Farrington, Elaine B Cadogan, Lucy C Riches, Antonio Garcia-Trinidad, Andrew G Thomason, Bhavika Patel, Jennifer Vincent, Alan Lau, Kurt G Pike, Thomas A Hunt, Amrita Sule, Nicholas C K Valerie, Laura Biddlestone-Thorpe, Jenna Kahn, Jason M Beckta, Nitai Mukhopadhyay, Bernard Barlaam, Sebastien L Degorce, Jason Kettle, Nicola Colclough, Joanne Wilson, Aaron Smith, Ian P Barrett, Li Zheng, Tianwei Zhang, Yingchun Wang, Kan Chen, Martin Pass, Stephen T Durant, Kristoffer Valerie
Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited CNS bioavailability, thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of lead compounds identified AZ31 and AZ32. The compounds were then tested in vivo for efficacy and impact on tumor and healthy brain...
May 16, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29768354/feasibility-and-effectiveness-of-electrochemical-dermal-conductance-measurement-for-the-screening-of-diabetic-neuropathy-in-primary-care-decoding-study-dermal-electrochemical-conductance-in-diabetic-neuropathy-rationale-and-design
#8
Juan J Cabré, Teresa Mur, Bernardo Costa, Francisco Barrio, Charo López-Moya, Ramon Sagarra, Montserrat García-Barco, Jesús Vizcaíno, Immaculada Bonaventura, Nicolau Ortiz, Gemma Flores-Mateo
Diabetes mellitus is the leading cause of polyneuropathy in the Western world. Diabetic neuropathy is a frequent complication of diabetes and may have great clinical transcendence due to pain and possible ulceration of the lower extremities. It is also a relevant cause of morbidity and mortality in patients with diabetes. Although the cause of polyneuropathy in patients with diabetes is only partially known, it has been associated with chronic hyperglycemia suggesting the possible etiopathogenic implication of advanced glycosylation end products...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29763272/colorectal-cancer-screening-and-prevention
#9
Thad Wilkins, Danielle McMechan, Asif Talukder
Colorectal cancer is a common cause of morbidity and mortality in the United States. Most colorectal cancers arise from preexisting adenomatous or serrated polyps. The incidence and mortality of colorectal cancer can be reduced with screening of average-risk adults 50 to 75 years of age. Randomized controlled trials show evidence of reduced colorectal cancer-specific mortality with guaiac-based fecal occult blood tests and flexible sigmoidoscopy. There are no randomized controlled trials on the effectiveness of colonoscopy to reduce colorectal cancer-specific mortality; however, several randomized controlled trials comparing colonoscopy with other strategies are in progress...
May 15, 2018: American Family Physician
https://www.readbyqxmd.com/read/29761007/behavioral-changes-induced-through-adenosine-a2a-receptor-ligands-in-a-rat-depression-model-induced-by-olfactory-bulbectomy
#10
Karla Margarita Padilla, Andres Quintanar-Setephano, Fabian López-Vallejo, Laura Cristina Berumen, Ricardo Miledi, Guadalupe García-Alcocer
Background: Major depressive disorders are characterized by their severity and long-lasting symptoms, which make such disorders highly disabling illnesses. Unfortunately, 50% of major depressive patients experience relapses, perhaps partly because drug research has been performed only in animal models that screen for antidepressant drugs that appear to only ameliorate acute depression symptoms. The bilateral olfactory bulbectomy (OBX) animal model presents the advantage of mimicking the symptoms of chronic depression by means of brain surgery...
May 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29744042/prevalence-and-patterns-of-drug-resistance-among-pulmonary-tuberculosis-patients-in-hangzhou-china
#11
Qingchun Li, Gang Zhao, Limin Wu, Min Lu, Wei Liu, Yifei Wu, Le Wang, Ke Wang, Han-Zhu Qian, Li Xie
Background: To evaluate prevalence and patterns of drug resistance among pulmonary tuberculosis (TB) patients in Hangzhou City, China. Methods: Sputum samples of smear positive TB patients enrolled in 2011 and 2015 were collected and tested for drug susceptibility, and demographic and medical record data were extracted from the electronic database of China Information System for Disease Control and Prevention. Chi-square test was used to compare drug resistance prevalence between new and treated patients and between male and female patients, and Chi-square test for trend was used to compare the prevalence over calendar years 2011 and 2015...
2018: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/29743134/validation-of-the-betastar-%C3%A2-advanced-for-tetracyclines-test-kit-for-the-screening-of-bulk-tank-and-tanker-truck-milks-for-the-presence-of-tetracycline-drug-residues
#12
David Ankrapp, Benjamin Schaus, Lauren Clements, Frank Klein, Jennifer Rice, John Rejman
A validation study was conducted for an immunochromatographic method (BetaStar® Advanced for Tetracyclines) for detection of tetracycline antibiotic residues in raw, commingled bovine milk. The assay was demonstrated to detect tetracycline, chlortetracycline, and oxytetracycline at levels below the FDA tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. Results of internal and independent laboratory dose-response studies employing spiked samples were in agreement...
May 9, 2018: Journal of AOAC International
https://www.readbyqxmd.com/read/29722441/systematic-review-safety-of-mesalazine-in-ulcerative-colitis
#13
REVIEW
P Sehgal, J-F Colombel, A Aboubakr, N Narula
BACKGROUND: Mesalazine is the most commonly prescribed medication for mild to moderate ulcerative colitis. It is generally well tolerated with some reported side effects. AIM: To summarise adverse drug events to mesalazine and recommend techniques for management. Furthermore, to determine if there is a dose-dependent relationship between high (>2.4 g/day) vs low dosing (≤2.4 g/day) and occurrence of adverse drug events. METHODS: A literature search for relevant studies from inception to 1 December 2017 of the MEDLINE database was conducted...
May 3, 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29718569/grp78-targeted-in-silico-virtual-screening-of-novel-anticancer-agents
#14
Ambily Nath Indu Viswanath, Ji Woong Lim, Seon Hee Seo, Jae Yeol Lee, Sang Min Lim, Ae Nim Pae
Overexpression of GRP78 in a variety of cancers such as glioblastoma, leukaemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in silico methods. As a first step towards the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore...
May 2, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29716784/emixustat-hydrochloride-for-geographic-atrophy-secondary-to-age-related-macular-degeneration-a-randomized-clinical-trial
#15
Philip J Rosenfeld, Pravin U Dugel, Frank G Holz, Jeffrey S Heier, Joel A Pearlman, Roger L Novack, Karl G Csaky, John M Koester, Jeffrey K Gregory, Ryo Kubota
PURPOSE: To determine whether emixustat hydrochloride (emixustat) reduces the rate of enlargement of geographic atrophy (GA) compared with placebo in subjects with age-related macular degeneration (AMD) and to evaluate the safety and tolerability of emixustat over 24 months of treatment. DESIGN: Multicenter, randomized, double-masked, placebo-controlled, phase 2b/3 clinical trial. PARTICIPANTS: Patients with GA secondary to AMD, a visual acuity score of at least 35 letters, and GA with a total area of 1...
April 28, 2018: Ophthalmology
https://www.readbyqxmd.com/read/29716553/protocol-for-a-cluster-randomised-controlled-trial-evaluating-the-impact-of-a-preschool-based-capacity-building-intervention-on-intimate-partner-violence-and-substance-misuse-in-sri-lanka
#16
Kamalini Lokuge, Polly Wallace, Kalini Subasinghe, Katherine Thurber, Tissa De Silva, Naomi Clarke, Dulshika Waas, Nisansala Liyanage, Udena Attygalle, Bradley Carron-Arthur, Kalyana Rodrigo, Emily Banks, Cate D'Este, Thilini Rajapakse
BACKGROUND: Past research has identified links between intimate partner violence (IPV) and alcohol misuse and poverty in Sri Lanka. Services that address substance misuse are amongst the few interventions shown to reduce IPV in settings similar to Sri Lanka. This paper describes the protocol for a study examining the impact of a preschool-based capacity building intervention on the prevalence of IPV and substance misuse in parents with children attending preschools, including uptake of available government services...
May 2, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29696202/efficacy-of-antiviral-drug-av2-in-the-treatment-of-human-papillomavirus-associated-precancerous-lesions-of-the-uterine-cervix-a-randomized-placebo-controlled-clinical-trial-in-kinshasa-dr-congo-kinvav-study
#17
Alex Baleka Mutombo, Rahma Tozin, Cindy Simoens, Ramokone Lisbeth, Johannes Bogers, Jean-Pierre Van Geertruyden, Yves Jacquemyn
Background: Cervical Cancer (CC) is a major public health problem in DR Congo; the high incidence of CC is due to the inexistence of effective screening programs based on cytology and/or HPV detection followed by appropriate treatments. This situation highlights the need to implement efficacious and inexpensive treatment methods. This study aims at evaluating the efficacy of a topical antiviral drug named AV2® as a treatment for HPV-associated lesions of the cervix. Methods: Women will undergo cytology sampling, HPV testing and Visual inspection of the cervix after application of 5% acetic acid (VIA)...
December 2017: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29692878/newly-diagnosed-hepatitis-c-in-the-us-commercially-insured-population-before-and-after-the-2012-implementation-of-expanded-screening-guidelines
#18
Bruce S Pyenson, Gabriela Dieguez, Christine Ferro, Maushumi Mavinkurve, Yuri Sanchez Gonzalez
Background: In the United States in 2014, more than 3 million individuals were estimated to have chronic hepatitis C virus (HCV) infection, including many undiagnosed individuals. In 2012, the Centers for Disease Control and Prevention expanded its HCV testing recommendations to target all adults born between 1945 and 1965, in addition to at-risk individuals, which has led to an increase in newly diagnosed patients. Few studies have explored the medical cost or clinical status of patients who are newly diagnosed with HCV...
February 2018: American Health & Drug Benefits
https://www.readbyqxmd.com/read/29685458/prevalence-of-drug-resistant-tuberculosis-and-imputed-burden-in-south-africa-a-national-and-sub-national-cross-sectional-survey
#19
Nazir Ahmed Ismail, Lindiwe Mvusi, Ananta Nanoo, Andries Dreyer, Shaheed V Omar, Sanni Babatunde, Thabo Molebatsi, Martie van der Walt, Adeboye Adelekan, Varough Deyde, Chikwe Ihekweazu, Shabir A Madhi
BACKGROUND: Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001-02 estimates. METHODS: A cross-sectional survey was done between June 15, 2012-June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa...
April 20, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29677524/effectiveness-of-community-based-depression-intervention-programme-comdip-to-manage-women-with-depression-in-primary-care-randomised-control-trial
#20
Pillaveetil Sathyadas Indu, Thekkethayyil Viswanathan Anilkumar, Krishnapillai Vijayakumar, K A Kumar, P Sankara Sarma, Saradamma Remadevi, Chittaranjan Andrade
BACKGROUND: In low and middle income countries where mental health resources are limited, community based depression intervention models, which can be implemented through the existing health system, are extremely relevant. OBJECTIVE: To test the effectiveness of Community based Depression Intervention Programme (ComDIP), newly developed by us, to reduce severity of depression in women, compared to the treatment as usual (TAU). METHODS: An RCT (Trial registration Number: CTRI/2011/08/001978, Clinical Trials Registry -India) was conducted in a primary care setting in Trivandrum, Kerala, South India...
April 2018: Asian Journal of Psychiatry
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