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https://www.readbyqxmd.com/read/28102767/synthesis-stereochemical-characterization-and-antimicrobial-evaluation-of-a-potentially-nonnephrotoxic-3-c-acethydrazide-puromycin-analog
#1
Josh Carter, Blair A Weaver, Maria A Chiacchio, Amy R Messersmith, Will E Lynch, Brent D Feske, Giuseppe Gumina
Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3'-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside...
January 19, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28102683/key-structural-elements-for-cellular-uptake-of-acinetobactin-a-major-siderophore-of-acinetobacter-baumannii
#2
Woon Young Song, Dawa Jeong, Jimin Kim, Min Wook Lee, Man Hwan Oh, Hak Joong Kim
Acinetobactin is a major siderophore utilized by the human pathogen Acinetobacter baumannii. The rapid acquisition of drug resistance by A. baumannii has garnered concern globally. Herein, acinetobactin and systematically generated analogues were prepared and characterized; the binding and cellular delivery of Fe(III) by the analogues were evaluated. This investigation not only led to the clarification of the physiologically relevant acinetobactin structure but also revealed several key structural elements for its functionality as a siderophore...
January 19, 2017: Organic Letters
https://www.readbyqxmd.com/read/28102676/novel-antitumor-platinum-ii-conjugates-containing-the-nonsteroidal-anti-inflammatory-agent-diclofenac-synthesis-and-dual-mechanisms-of-antiproliferative-effects
#3
Francesco Paolo Intini, Juraj Zajac, Vojtech Novohradsky, Teresa Saltarella, Concetta Pacifico, Viktor Brabec, Giovanni Natile, Jana Kasparkova
One concept how to improve anticancer effects of conventional metallodrugs consists in conjugation of these compounds with other biologically (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, biological effects, and mechanisms of action of new Pt(II) derivatives containing one or two nonsteroidal anti-inflammatory diclofenac (DCF) ligands also known for their antitumor effects. The antiproliferative properties of these metallic conjugates show that these compounds are potent and cancer cell selective cytotoxic agents exhibiting activity in cisplatin resistant and the COX-2 positive tumor cell lines...
January 19, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28102520/us-fda-perspective-on-elbasvir-grazoprevir-treatment-for-patients-with-chronic-hepatitis-c-virus-genotype-1-or-4-infection
#4
Sarita D Boyd, LaRee Tracy, Takashi E Komatsu, Patrick R Harrington, Prabha Viswanathan, Jeff Murray, Adam Sherwat
Elbasvir/grazoprevir demonstrated high sustained virologic response rates 12 weeks after the end of treatment (SVR12) across five clinical trials in subjects infected with chronic hepatitis C virus (HCV) genotype 1, including those with advanced chronic kidney disease (CKD), and GT4. Despite favorable results overall, the US Food and Drug Administration (FDA) encountered challenging regulatory issues due to the limitations of clinical trial data in certain subpopulations. In GT1a-infected subjects, baseline NS5A resistance-associated polymorphisms emerged as the strongest baseline characteristic associated with diminished SVR12 rates following 12 weeks of elbasvir/grazoprevir treatment...
January 19, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28101802/cold-pcr-technologies-in-the-area-of-personalized-medicine-methodology-and-applications
#5
REVIEW
Florence Mauger, Alexandre How-Kit, Jörg Tost
Somatic mutations bear great promise for use as biomarkers for personalized medicine, but are often present only in low abundance in biological material and are therefore difficult to detect. Many assays for mutation analysis in cancer-related genes (hotspots) have been developed to improve diagnosis, prognosis, prediction of drug resistance, and monitoring of the response to treatment. Two major approaches have been developed: mutation-specific amplification methods and methods that enrich and detect mutations without prior knowledge on the exact location and identity of the mutation...
January 18, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28101785/acinetobacter-baumannii-bacteraemia-in-patients-with-haematological-malignancy-a-multicentre-retrospective-study-from-the-infection-working-party-of-jiangsu-society-of-hematology
#6
X Wang, L Zhang, A Sun, X Yang, W Sang, Y Jiang, J Cheng, J Wang, M Zhou, B Chen, J Ouyang
Acinetobacter baumannii (Ab) bacteraemia in patients with haematological malignancies is fatal but rarely reported. We explored the clinical characteristics, drug resistances and prognostic factors in these patients. This multicentre, retrospective study was conducted at the department of haematology wards of 18 tertiary hospitals in China from January 2014 to June 2015. The total clinical isolates from every source were collected from patients with haematological malignancy. Haematological malignancy patients diagnosed with Ab bacteraemia were analysed...
January 18, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28101479/excessive-daytime-sleepiness-and-sleep-disorders-in-a-population-of-patients-with-epilepsy-a-case-control-study
#7
Matilde Gammino, Leila Zummo, Anna Lo Bue, Lidia Urso, Valeria Terruso, Oreste Marrone, Brigida Fierro, Ornella Daniele
BACKGROUND AND PURPOSE: There are several primary causes for excessive daytime sleepiness (EDS) and sleep disorders in patients with epilepsy. Up to now, studies in the literature report conflicting data in terms of both prevalence and aetiology. The aim of our study was therefore to evaluate the prevalence of EDS and some sleep disorders in a population of patients with epilepsy treated with no more than two antiepileptic drugs (AEDs). We also investigated the role of the depression of mood as a variable that can negatively affect EDS...
December 2016: Journal of Epilepsy Research
https://www.readbyqxmd.com/read/28101344/evaluation-of-pharmacological-relaxation-effect-of-the-natural-product-naringin-on-in-vitro-cultured-airway-smooth-muscle-cells-and-in-vivo-ovalbumin-induced-asthma-balb-c-mice
#8
Yue Wang, Yun Lu, Mingzhi Luo, Xiaohao Shi, Yan Pan, Huilong Zeng, Linhong Deng
Asthma has become a common chronic respiratory disease worldwide and its prevalence is predicted to continue increasing in the next decade, particularly in developing countries. A key component in asthma therapy is to alleviate the excessive bronchial airway narrowing ultimately due to airway smooth muscle contraction, which is often facilitated by a smooth muscle relaxant, such as the β2-adrenergic agonists. Recently, bitter taste receptor (TAS2R) agonists, including saccharin and chloroquine, have been found to potently relax the airway smooth muscle cells (ASMCs) via intracellular Ca(2+) signaling...
December 2016: Biomedical Reports
https://www.readbyqxmd.com/read/28101198/elevated-expression-of-nrf2-mediates-multidrug-resistance-in-cd133-head-and-neck-squamous-cell-carcinoma-stem-cells
#9
Bao-Cai Lu, Jing Li, Wen-Fa Yu, Guo-Zheng Zhang, Hui-Min Wang, Hui-Min Ma
Enhanced expression of the ATP-binding cassette (ABC) transporter protein ABC sub-family G member 2 (ABCG2) in cancer stem cells (CSCs) plays a major role in chemotherapeutic drug efflux, which results in therapy failure and tumor relapse. In addition to downregulating apoptosis in CSCs, it has been reported that the transcriptional upregulation of the redox sensing factor Nrf2 is involved in the upregulation of ABCG2 expression and consequent chemoresistance. The current study investigated the presence of cancer stem-like side population (SP) cells from head and neck squamous cell carcinoma (HNSCC) samples, and evaluated the Nrf2 expression profile and multidrug resistance properties of HNSCC stem cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101195/combinations-in-multimodality-treatments-and-clinical-outcomes-during-cancer
#10
Xiao-Ying Zhang, Pei-Ying Zhang
Combination approach could be easily considered as the future of therapeutics in all pathological states including cancer. Scientists are trying different combinations in order to determine synergism among different therapeutics which ultimately helps in the improved and more efficient management of the affected patients. Combination of multi-chemotherapeutic agents, or multi-drug therapy, may be the most commonly used strategy for cancer treatment. Monotherapy causes drug resistance and loses its response in patients after several cycles of treatment...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28100891/reverse-right-ventricular-remodeling-after-lung-transplantation-in-patients-with-pulmonary-arterial-hypertension-under-combination-therapy-of-targeted-medical-drugs
#11
Toshihiro Sarashina, Kazufumi Nakamura, Satoshi Akagi, Takahiro Oto, Hiroki Oe, Kentaro Ejiri, Koji Nakagawa, Nobuhiro Nishii, Hiromi Matsubara, Motomu Kobayashi, Hiroshi Morimatsu, Shinichiro Miyoshi, Hiroshi Ito
BACKGROUND: Patients with pulmonary arterial hypertension (PAH) are currently treated with combination therapy of PAH-targeted drugs. Reverse right ventricular (RV) remodeling after lung transplantation (LTx) in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.Methods and Results:A total of 136 patients, including 32 with PAH, underwent LTx from 1998 to 2014. We enrolled 12 consecutive patients with PAH treated with combination therapy of PAH-targeted drugs who underwent LTx and retrospectively analyzed the temporal and serial changes in hemodynamics and echocardiography before LTx and at 3 and 12 months after LTx...
January 18, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28100602/find-tuberculosis-strain-bank-a-resource-for-researchers-and-developers-working-on-tests-to-detect-mycobacterium-tuberculosis-and-related-drug-resistance
#12
Belay Tessema, Pamela Nabeta, Eloise Valli, Audrey Albertini, Jimena Collantes, Nguyen Huu Lan, Elena Romancenco, Nestani Tukavdze, Claudia M Denkinger, David L Dolinger
BACKGROUND: The spread of multidrug-resistant tuberculosis and extensively drug-resistant TB hampers the global efforts in the fight against tuberculosis. To enhance the development and evaluation of diagnostic tests quickly and efficiently, well characterized strains and samples from drug resistant tuberculosis patients are necessary. In this project, FIND has focused on the collection, characterization and storage of such well-characterized reference materials and to make them available to researchers and developers...
January 18, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28100546/accuracy-of-line-probe-assays-for-the-diagnosis-of-pulmonary-and-multidrug-resistant-tuberculosis-a-systematic-review-and-meta-analysis
#13
Ruvandhi R Nathavitharana, Patrick G T Cudahy, Samuel G Schumacher, Karen R Steingart, Madhukar Pai, Claudia M Denkinger
Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed.This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing...
January 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28100438/high-dose-rifampicin-moxifloxacin-and-sq109-for-treating-tuberculosis-a-multi-arm-multi-stage-randomised-controlled-trial
#14
Martin J Boeree, Norbert Heinrich, Rob Aarnoutse, Andreas H Diacon, Rodney Dawson, Sunita Rehal, Gibson S Kibiki, Gavin Churchyard, Ian Sanne, Nyanda E Ntinginya, Lilian T Minja, Robert D Hunt, Salome Charalambous, Madeleine Hanekom, Hadija H Semvua, Stellah G Mpagama, Christina Manyama, Bariki Mtafya, Klaus Reither, Robert S Wallis, Amour Venter, Kim Narunsky, Anka Mekota, Sonja Henne, Angela Colbers, Georgette Plemper van Balen, Stephen H Gillespie, Patrick P J Phillips, Michael Hoelscher
BACKGROUND: Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. METHODS: We did a randomised controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15-20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15-20 mg/kg ethambutol)...
January 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28100327/-intermittent-convulsions-for-1-5-years-and-psychomotor-retardation-in-a-girl
#15
Li Yang, Yu-Fen Li, Li-Yun Xu, Na Xu, Yu-Zeng Han, Jun-Lin Wang, Ji-Guo Song, Ying Hua, Li-Ping Zhu
The study reports a girl with pyridoxine-dependent epilepsy. The girl was admitted at the age of 2 years because of intermittent convulsions for 1.5 years and psychomotor retardation. She had a history of "hypoxia" in the neonatal period. At the age of 5 months recurrent epileptic seizures occurred. The child was resistant to antiepileptic drugs, and had many more seizures when she got cold or fever. She also had a lot of convulsive status epilepticus. No discharges were found during several video-EEG monitorings...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28100241/personalized-life-expectancy-and-treatment-benefit-index-of-antiretroviral-therapy
#16
Yanni Xiao, Xiaodan Sun, Sanyi Tang, Yicang Zhou, Zhihang Peng, Jianhong Wu, Ning Wang
BACKGROUND: The progression of Human Immunodeficiency Virus (HIV) within host includes typical stages and the Antiretroviral Therapy (ART) is shown to be effective in slowing down this progression. There are great challenges in describing the entire HIV disease progression and evaluating comprehensive effects of ART on life expectancy for HIV infected individuals on ART. METHODS: We develop a novel summative treatment benefit index (TBI), based on an HIV viral dynamics model and linking the infection and viral production rates to the Weibull function...
January 18, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/28099902/anthelmintic-mebendazole-enhances-cisplatin-s-effect-on-suppressing-cell-proliferation-and-promotes-differentiation-of-head-and-neck-squamous-cell-carcinoma-hnscc
#17
Fugui Zhang, Yong Li, Hongmei Zhang, Enyi Huang, Lina Gao, Wenping Luo, Qiang Wei, Jiaming Fan, Dongzhe Song, Junyi Liao, Yulong Zou, Feng Liu, Jianxiang Liu, Jiayi Huang, Dan Guo, Chao Ma, Xue Hu, Li Li, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Tingting Wu, Hue H Luu, Rex C Haydon, Jinlin Song, Tong-Chuan He, Ping Ji
Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099900/skeletal-muscle-aging-influence-of-oxidative-stress-and-physical-exercise
#18
REVIEW
Mariana Janini Gomes, Paula Felippe Martinez, Luana Urbano Pagan, Ricardo Luiz Damatto, Marcelo Diacardia Mariano Cezar, Aline Regina Ruiz Lima, Katashi Okoshi, Marina Politi Okoshi
Skeletal muscle abnormalities are responsible for significant disability in the elderly. Sarcopenia is the main alteration occurring during senescence and a key public health issue as it predicts frailty, poor quality of life, and mortality. Several factors such as reduced physical activity, hormonal changes, insulin resistance, genetic susceptibility, appetite loss, and nutritional deficiencies are involved in the physiopathology of muscle changes. Sarcopenia is characterized by structural, biochemical, molecular and functional muscle changes...
January 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099825/transmission-of-extensively-drug-resistant-tuberculosis-in-south-africa
#19
N Sarita Shah, Sara C Auld, James C M Brust, Barun Mathema, Nazir Ismail, Pravi Moodley, Koleka Mlisana, Salim Allana, Angela Campbell, Thuli Mthiyane, Natashia Morris, Primrose Mpangase, Hermina van der Meulen, Shaheed V Omar, Tyler S Brown, Apurva Narechania, Elena Shaskina, Thandi Kapwata, Barry Kreiswirth, Neel R Gandhi
Background Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. Methods We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014...
19, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28099785/a-dual-topoisomerase-inhibitor-of-intense-pro-apoptotic-and-antileukemic-nature-for-cancer-treatment
#20
Christopher Meier, Tamara N Steinhauer, Fabian Koczian, Birte Plitzko, Katharina Jarolim, Ulrich Girreser, Simone Braig, Doris Marko, Angelika M Vollmar, Bernd Clement
Classic cytotoxic drugs constantly remain an indispensable instrument in antitumor therapy due to their effectiveness and a more prevalent insensibility against tumor resistance mechanisms. We describe the favorable properties of P8-D6, a powerful inductor of apoptosis caused by an equipotent inhibition of human topoisomerase I and II activities. A broad spectrum effect against human tumor cell lines in nanomolar concentrations as well as strong anti-leukemic effects were shown and proven to be superior to marketed topo-targeting drugs and dual topoisomerase inhibitors in clinical trials...
January 18, 2017: ChemMedChem
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