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drug testing

Anna Wallerstedt, Peter Strom, Henrik Gronberg, Tobias Nordstrom, Martin Eklund
Background: Studies have shown that 5α-reductase inhibitors (5-ARIs) decrease the risk for low-grade prostate cancer (PC), but results are conflicting concerning high-grade PCs. The objective of the present study is to evaluate the association between 5-ARI treatment for lower urinary tract symptoms and the risk for PC. Methods: This is a population-based prospective study on all men age 40 years and older with at least one prostate-specific antigen (PSA) test in Stockholm County from January 2007 until December 2015...
March 14, 2018: Journal of the National Cancer Institute
Gregory D Bowden, Kirkwood M Land, Roberta M O'Connor, Heather M Fritz
The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S...
February 16, 2018: International Journal for Parasitology, Drugs and Drug Resistance
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Jana Tchekalarova, Keylla da Conceição Machado, Antonio Luiz Gomes Júnior, Ana Amélia de Carvalho Melo Cavalcante, Albena Momchilova, Rumyana Tzoneva
PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test...
March 12, 2018: Seizure: the Journal of the British Epilepsy Association
Navaneetha Santhanam, Lee Kumanchik, Xiufang Guo, Frank Sommerhage, Yunqing Cai, Max Jackson, Candace Martin, George Saad, Christopher W McAleer, Ying Wang, Andrea Lavado, Christopher J Long, James J Hickman
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...
February 27, 2018: Biomaterials
Andrew McDowell, Neeraj Raizada, Sunil D Khaparde, Raghuram Rao, Sanjay Sarin, Aakshi Kalra, Virender Singh Salhotra, Sreenivas Achuthan Nair, Catharina Boehme, Claudia M Denkinger
BACKGROUND: Diagnosing tuberculosis (TB) in children presents considerable challenges. Upfront testing on Xpert® MTB/RIF ('Xpert')-a rapid molecular assay with high sensitivity and specificity-for pediatric presumptive TB patients, as recommended by India's Revised National Tuberculosis Control Program (RNTCP), can pave the way for early TB diagnosis. As part of an ongoing project implemented by Foundation for Innovative New Diagnostics (FIND) dedicated to providing upfront free-of-cost (FOC) Xpert testing to children seeking care in the public and private sectors, a qualitative assessment was designed to understand how national guidelines on TB diagnosis and Xpert technology have been integrated into the pediatric TB care practices of different health providers...
2018: PloS One
Rogério M Pinto, Susan S Witte, Prema L Filippone, C Jean Choi, Melanie Wall
The U.S. Centers for Disease Control and Prevention (CDC) Diffusion of Effective Behavioral Interventions project has disseminated HIV behavioral interventions (EBIs) across the United States since the 1990s. In 2011, the CDC launched the High-Impact HIV Prevention (HIP) project, providing EBIs plus high-impact services (HIV testing, primary care, and support services). Providers (nurses, social workers, educators) are unable to consistently make linkages; thus, numerous at-risk individuals are not benefitting from HIP...
March 1, 2018: Health Education & Behavior: the Official Publication of the Society for Public Health Education
Lucia Romero, Jordi Cano, Julio Gomis-Tena, Beatriz Trenor, Ferran Sanz, Manuel Pastor, Javier Saiz
Drug-induced proarrhythmicity is a major concern for regulators and pharmaceutical companies. For novel drug candidates, the standard assessment involves the evaluation of the potassium hERG channels block and the in vivo prolongation of the QT interval. However, this method is known to be too restrictive and to stop the development of potentially valuable therapeutic drugs. The aim of this work is to create an in silico tool for early detection of drug-induced proarrhythmic risk. The system is based on simulations of how different compounds affect the action potential duration (APD) of isolated endocardial, midmyocardial, and epicardial cells as well as the QT prolongation in a virtual tissue...
March 16, 2018: Journal of Chemical Information and Modeling
Julian D Ford, Ruby Charak, Crosby A Modrowski, Patricia K Kerig
Polyvictimization (PV) has been shown to be associated with psychosocial and behavioral impairment in community and high risk populations, including youth involved in juvenile justice. However, the mechanisms accounting for these adverse outcomes have not been empirically delineated. Symptoms of posttraumatic stress disorder (PTSD) and dissociation are documented sequelae of PV and are associated with a wide range of behavioral/emotional problems. This study used a cross-sectional research design and bootstrapped multiple mediation analyses with self-report measures completed by a large sample of justice-involved youth (N = 809, ages 12-19 years old, 27% female, 46...
May 2018: Journal of Trauma & Dissociation
Ye Seul Yang, Min Hyuk Lim, Seong Ok Lee, Eun Roh, Chang Ho Ahn, Soo Heon Kwak, Young Min Cho, Sungwan Kim, Andrea Mari, Kyong Soo Park, Hye Seung Jung
AIMS: Angiotensin receptor blockers (ARB) are anti-hypertensive drugs with renal protective effect. Additionally, they have been associated with the delayed onset of type 2 diabetes in high-risk populations, and some ARB were reported to increase insulin secretion and sensitivity in patients with prediabetes. Therefore, we studied the effects of ARB on insulin secretion in hypertensive patients with type 2 diabetes. MATERIALS AND METHODS: Forty-one patients were enrolled in this open-labeled, active comparator-controlled and crossover study...
March 15, 2018: Diabetes, Obesity & Metabolism
Andrea J Santamaría, Juan P Solano, Francisco D Benavides, James D Guest
Cell transplant-mediated tissue repair of the damaged spinal cord is being tested in several clinical trials. The current candidates are neural stem cells, stromal cells, and autologous Schwann cells (aSC). Due to their peripheral origin and limited penetration of astrocytic regions, aSC are transplanted intralesionally as compared to neural stem cells that are transplanted into intact spinal cord. Injections into either location can cause iatrogenic injury, and thus technical precision is important in the therapeutic risk-benefit equation...
2018: Methods in Molecular Biology
Hai Yan Huang, Shao Jian Lin, Wei Guo Zhao, Zhe Bao Wu
The aim of this study is to compare the efficacy of bromocriptine (BRC) versus cabergoline (CAB) in patients with giant prolactinomas. We searched MEDLINE, EMBASE, CENTRAL and Clinical for studies dated before March 1st, 2016, that used BRC or CAB for the treatment of patients with giant prolactinomas. Specific eligibility criteria were set to identify articles and cases. The selected articles were reviewed, and the data were extracted for analysis. The compared outcomes included tumor shrinkage, tumor response, normalization of prolactin (PRL) level, and visual field defect (VFD) improvement...
March 15, 2018: Metabolic Brain Disease
Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
March 15, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Beatriz V R Pereira, Gregorio Nolazco Matus, Monica Jones Costa, André Cordeiro Alves Dos Santos, Elaine C M Silva-Zacarin, Janaina Braga do Carmo, Bruno Nunes
Over time, many pollutants of anthropogenic origin have caused the contamination of aquatic ecosystems. Among several characteristics, these compounds can reach the trophic chain, causing deleterious interactions with the biota. Pharmaceutical substances can be included in this scenario as emerging contaminants that reach the aquatic environment because of direct human and veterinary usage, and release by industrial effluents, as well as through domestic dumping of surplus drugs. The effects of these compounds on exposed organisms have been studied since the 1990s, but ecotoxicological data for such chemicals are still scarce especially concerning aquatic organisms from tropical regions...
March 15, 2018: Environmental Science and Pollution Research International
Kaimin Lu, Xin Wang, Yuyu Chen, Danfeng Liang, Hao Luo, Li Long, Zongyue Hu, Jinku Bao
Osteosarcoma is the most common primary malignant bone tumor among adolescents worldwide with high mortality rate. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine kinase and is considered as a validated target in osteosarcoma therapy. Therefore, the study of GSK3β inhibitors is one of the most popular fields in anti-osteosarcoma drug development. Here, the tools of bioinformatics were used to screen novel effective inhibitors of GSK3β from ZINC Drug Database. The molecular docking, molecular dynamic simulations, MM/GBSA, and energy decomposition analysis were performed to identify the inhibitors...
March 13, 2018: Acta Biochimica et Biophysica Sinica
Jason T C Lee, Iryna Shanina, Yung Ning Chu, Marc S Horwitz, James D Johnson
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14...
March 15, 2018: Scientific Reports
Shefali Setia Verma, Navya Josyula, Anurag Verma, Xinyuan Zhang, Yogasudha Veturi, Frederick E Dewey, Dustin N Hartzel, Daniel R Lavage, Joe Leader, Marylyn D Ritchie, Sarah A Pendergrass
The DrugBank database consists of ~800 genes that are well characterized drug targets. This list of genes is a useful resource for association testing. For example, loss of function (LOF) genetic variation has the potential to mimic the effect of drugs, and high impact variation in these genes can impact downstream traits. Identifying novel associations between genetic variation in these genes and a range of diseases can also uncover new uses for the drugs that target these genes. Phenome Wide Association Studies (PheWAS) have been successful in identifying genetic associations across hundreds of thousands of diseases...
March 15, 2018: Scientific Reports
Bhupesh Bagga, Savitri Sharma, Sai Jeevan Madhuri Guda, Ritu Nagpal, Joveeta Joseph, Kodiganti Manjulatha, Ashik Mohamed, Prashant Garg
BACKGROUND: Pythium insidiosum is a parafungus that causes keratitis resembling fungal keratitis. This study compares outcome in a large cohort of patients with P insidiosum keratitis treated with antifungal drugs, to a pilot group treated with antibacterial antibiotics. METHODS: Between January 2014 and December 2016, 114 patients with culture positive P insidiosum keratitis were included in the study. A subset of culture isolates was tested in vitro for response to nine antibacterial antibiotics by disc diffusion and E test...
March 15, 2018: British Journal of Ophthalmology
Sanghamitra Mohanty, Prasant Mohanty, Chintan Trivedi, Carola Gianni, Domenico G Della Rocca, Luigi Di Biase, Andrea Natale
BACKGROUND: This meta-analysis systematically evaluated the outcome of pulmonary vein isolation (PVI) with and without focal impulse and rotor modulation (FIRM) ablation in patients with atrial fibrillation. METHODS AND RESULTS: Extensive literature search was performed for studies reporting outcomes of PVI alone and PVI+FIRM procedures. For PVI alone, only randomized trials conducted in the past 3 years reporting single-procedure off-antiarrhythmic drugs success rate at ≥12-month follow-up were included...
March 2018: Circulation. Arrhythmia and Electrophysiology
Alejandra Nieto, Holger Roehl
There has been a growing interest in recent years in the assessment of suitable vial/stopper combinations for storage and shipment of frozen drug products. Considering that the glass transition temperature (Tg) of butyl rubber stoppers used in Container Closure Systems (CCS) is between -55°C to -65°C, a storage or shipment temperature of a frozen product below the Tg of the rubber stopper, may require special attention, since below the Tg the rubber becomes more plastic-like and loses its elastic (sealing) characteristics...
March 15, 2018: PDA Journal of Pharmaceutical Science and Technology
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