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https://www.readbyqxmd.com/read/28927987/industry-perspective-on-contemporary-protein-binding-methodologies-considerations-for-regulatory-drug-drug-interaction-and-related-guidelines-on-highly-bound-drugs
#1
REVIEW
Li Di, Christopher Breen, Rob Chambers, Sean T Eckley, Robert Fricke, Avijit Ghosh, Paul Harradine, J Cory Kalvass, Stacy Ho, Caroline A Lee, Punit Marathe, Everett J Perkins, Mark Qian, Susanna Tse, Zhengyin Yan, Maciej J Zamek-Gliszczynski
Regulatory agencies have recently issued drug-drug interaction (DDI) guidelines, which require determination of plasma protein binding (PPB). To err on the conservative side, the agencies recommend that a 0.01 lower limit of fraction unbound (fu) be used for highly bound compounds (>99%), irrespective of the actual measured values. While this may avoid false negatives, the recommendation would likely result in a high rate of false positive predictions, resulting in unnecessary clinical studies and more stringent inclusion/exclusion criteria, which may add cost and time in delivery of new medicines to patients...
September 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28925920/low-radon-exposure-and-mortality-among-jouac-uranium-miners-an-update-of-the-french-cohort-1946-2007
#2
Estelle Rage, Sylvaine Caër-Lorho, Dominique Laurier
After the extension of the French cohort of uranium miners with the inclusion of workers employed in the Jouac mines, this article seeks to describe the new Jouac cohort and to estimate mortality risks, as well as to quantify their relation to radon exposure in this extended cohort. The Jouac cohort includes 458 miners hired by the Société des Mines de Jouac between 1957 and 2001. As there is no measurement of radon exposure before 1978 were unavailable, only the post-1977 Jouac cohort (n=314) has been included in the French cohort, creating an extended cohort of 5400 French uranium miners followed up from 1946 to 2007...
September 19, 2017: Journal of Radiological Protection: Official Journal of the Society for Radiological Protection
https://www.readbyqxmd.com/read/28916844/left-sided-breast-cancer-and-risks-of-secondary-lung-cancer-and-ischemic-heart-disease-effects-of-modern-radiotherapy-techniques
#3
Stefanie Corradini, Hendrik Ballhausen, Helmut Weingandt, Philipp Freislederer, Stephan Schönecker, Maximilian Niyazi, Cristoforo Simonetto, Markus Eidemüller, Ute Ganswindt, Claus Belka
PURPOSE: Modern breast cancer radiotherapy techniques, such as respiratory-gated radiotherapy in deep-inspiration breath-hold (DIBH) or volumetric-modulated arc radiotherapy (VMAT) have been shown to reduce the high dose exposure of the heart in left-sided breast cancer. The aim of the present study was to comparatively estimate the excess relative and absolute risks of radiation-induced secondary lung cancer and ischemic heart disease for different modern radiotherapy techniques. METHODS: Four different treatment plans were generated for ten computed tomography data sets of patients with left-sided breast cancer, using either three-dimensional conformal radiotherapy (3D-CRT) or VMAT, in free-breathing (FB) or DIBH...
September 15, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28912098/melatonin-mediated-upregulation-of-sirt3-attenuates-sodium-fluoride-induced-hepatotoxicity-by-activating-the-mt1-pi3k-akt-pgc-1%C3%AE-signaling-pathway
#4
Chao Song, Jiamin Zhao, Beibei Fu, Dan Li, Tingchao Mao, Wei Peng, Haibo Wu, Yong Zhang
Mitochondrial reactive oxygen species (ROS) production has been implicated in the pathogenesis of fluoride toxicity in liver. Melatonin, an indolamine synthesized in the pineal gland, was previously shown to protect against sodium fluoride (NaF)-induced hepatotoxicity. This study investigated the protective effects of melatonin pretreatment on NaF-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Reducing mitochondrial ROS by melatonin substantially attenuated NaF-induced NADPH oxidase 4 (Nox4) upregulation and cytotoxicity in L-02 cells...
September 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28905163/data-sharing-mandates-developmental-science-and-responsibly-supporting-authors
#5
EDITORIAL
Roger J R Levesque
Data sharing has come of age. Long expected as a professional courtesy but rarely honored, data sharing is now highlighted in codes of ethics, supported by research communities, required by leading funding organizations, and variously encouraged and mandated by journals and even publishers. These developments reveal how sharing generates many benefits, all of which go to the integrity of the scientific process. Yet, sharing remains a complex phenomenon. This Editorial explains the journal's response to the publisher's mandate to establish an appropriate data sharing policy for the Journal of Youth and Adolescence...
September 13, 2017: Journal of Youth and Adolescence
https://www.readbyqxmd.com/read/28883902/sirt1-activation-by-resveratrol-alleviates-cardiac-dysfunction-via-mitochondrial-regulation-in-diabetic-cardiomyopathy-mice
#6
Sai Ma, Jing Feng, Ran Zhang, Jiangwei Chen, Dong Han, Xiang Li, Bo Yang, Xiujuan Li, Miaomiao Fan, Congye Li, Zuhong Tian, Yabin Wang, Feng Cao
BACKGROUND: Diabetic cardiomyopathy (DCM) is a major threat for diabetic patients. Silent information regulator 1 (SIRT1) has a regulatory effect on mitochondrial dynamics, which is associated with DCM pathological changes. Our study aims to investigate whether resveratrol, a SRIT1 activator, could exert a protective effect against DCM. METHODS AND RESULTS: Cardiac-specific SIRT1 knockout (SIRT1(KO)) mice were generated using Cre-loxP system. SIRT1(KO) mice displayed symptoms of DCM, including cardiac hypertrophy and dysfunction, insulin resistance, and abnormal glucose metabolism...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28873144/correcting-the-medical-literature-to-err-is-human-to-correct-divine
#7
Stacy Christiansen, Annette Flanagin
No abstract text is available yet for this article.
September 5, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28872271/to-err-is-human-to-correct-is-public-health-a-systematic-review-examining-poor-quality-testing-and-misdiagnosis-of-hiv-status
#8
Cheryl C Johnson, Virginia Fonner, Anita Sands, Nathan Ford, Carla Mahklouf Obermeyer, Sharon Tsui, Vincent Wong, Rachel Baggaley
INTRODUCTION: In accordance with global testing and treatment targets, many countries are seeking ways to reach the "90-90-90" goals, starting with diagnosing 90% of all people with HIV. Quality HIV testing services are needed to enable people with HIV to be diagnosed and linked to treatment as early as possible. It is essential that opportunities to reach people with undiagnosed HIV are not missed, diagnoses are correct and HIV-negative individuals are not inadvertently initiated on life-long treatment...
August 29, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28864027/efficacy-and-safety-of-tribendimidine-tribendimidine-plus-ivermectin-tribendimidine-plus-oxantel-pamoate-and-albendazole-plus-oxantel-pamoate-against-hookworm-and-concomitant-soil-transmitted-helminth-infections-in-tanzania-and-c%C3%A3-te-d-ivoire-a-randomised-controlled
#9
Wendelin Moser, Jean T Coulibaly, Said M Ali, Shaali M Ame, Amour K Amour, Richard B Yapi, Marco Albonico, Maxim Puchkov, Jörg Huwyler, Jan Hattendorf, Jennifer Keiser
BACKGROUND: Preventive chemotherapy is the current strategy to control soil-transmitted helminth infections (caused by Ascaris lumbricoides, hookworm, and Trichuris trichiura). But, to improve efficacy and avoid emerging resistance, new drugs are warranted. Tribendimidine has shown good anthelmintic efficacy and is therefore a frontrunner for monotherapy and combination chemotherapy. METHODS: We did a randomised, controlled, single-blinded, non-inferiority trial on Pemba Island, Tanzania, and in Côte d'Ivoire...
August 29, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28846644/the-mediating-role-of-psychological-capital-on-the-association-between-occupational-stress-and-job-satisfaction-among-township-cadres-in-a-specific-province-of-china-a-cross-sectional-study
#10
Chang-Yue Shang Guan, Yu Li, Hong-Lin Ma
Background: Township cadres, considered as basic executors of state policy, play an important role in Chinese society. Their job satisfaction is a vital issue for township management, but there are few studies on this topic in China. The goal of this study is to analyze the relationship between occupational stress and job satisfaction, and to further examine whether psychological capital (PsyCap) can serve as a mediator between stress and job satisfaction in Chinese township cadres. Methods: A cross-sectional survey was carried out during the period of from October 2015 to January 2016 in Liaoning Province of China...
August 28, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28841353/esrra-estrogen-related-receptor-alpha-is-a-key-coordinator-of-transcriptional-and-post-translational-activation-of-autophagy-to-promote-innate-host-defense
#11
Soo Yeon Kim, Chul-Su Yang, Hye-Mi Lee, Jin Kyung Kim, Yi-Sak Kim, Ye-Ram Kim, Jae-Sung Kim, Tae Sung Kim, Jae-Min Yuk, Catherine Rosa Dufour, Sang-Hee Lee, Jin-Man Kim, Hueng-Sik Choi, Vincent Giguère, Eun-Kyeong Jo
The orphan nuclear receptor ESSRA (estrogen related receptor, alpha) is a key regulator of energy homeostasis and mitochondrial function. Macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. Here, we demonstrate that ESRRA is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. AMP-activated protein kinase pathway and SIRT1 (sirtuin 1) activation led to induction of ESRRA, which is essential for autophagosome formation, in bone marrow-derived macrophages...
August 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28820402/does-signaling-of-estrogen-related-receptors-affect-structure-and-function-of-bank-vole-leydig-cells
#12
P Pawlicki, A Milon, M Zarzycka, J Galas, W Tworzydlo, A Kaminska, L Pardyak, K Lesniak, A Pacwa, B Bilinska, E Gorowska-Wojtowicz, M Kotula-Balak
To get a deeper insight into the function of estrogen-related receptors (ERRs) and dissect underlying mechanism in Leydig cells, ERRs (type α, β and γ) were blocked or activated in testes of adult bank voles (Myodes glareolus) which show seasonal changes in the intratesticular sex hormones level. Both actively reproducing animals (long day conditions; LD) and those with regression of the reproductive system (short day conditions; SD) received intraperitoneal injections of selective ERRα antagonist 3-[4-(2,4-Bis-trifluoromethylbenzyloxy)-3-methoxyphenyl]-2-cyano-N-(5-trifluoromethyl-1,3,4-thiadiazol-2-yl)acrylamide (XCT 790) or selective ERRβ/ERRγ agonist N-(4-(Diethylaminobenzylidenyl)-N'-(4-hydroxybenzoyl)-hydrazine (DY131) (50 μ/kg bw; six doses every other day)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28804711/annotation-of-the-nuclear-receptors-in-an-estuarine-fish-species-fundulus-heteroclitus
#13
William S Baldwin, W Tyler Boswell, Gautam Ginjupalli, Elizabeth J Litoff
The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28780078/atp-maintenance-via-two-types-of-atp-regulators-mitigates-pathological-phenotypes-in-mouse-models-of-parkinson-s-disease
#14
Masaki Nakano, Hiromi Imamura, Norio Sasaoka, Masamichi Yamamoto, Norihito Uemura, Toshiyuki Shudo, Tomohiro Fuchigami, Ryosuke Takahashi, Akira Kakizuka
Parkinson's disease is assumed to be caused by mitochondrial dysfunction in the affected dopaminergic neurons in the brain. We have recently created small chemicals, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption. By contrast, agonistic ligands of ERRs (estrogen receptor-related receptors) are expected to raise cellular ATP levels via enhancing ATP production. Here, we show that esculetin functions as an ERR agonist, and its addition to culture media enhances glycolysis and mitochondrial respiration, leading to elevated cellular ATP levels...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28715276/cancer-incidence-after-in-utero-exposure-to-ionizing-radiation-in-techa-river-residents
#15
L Yu Krestinina, Yu E Kharyuzov, S B Epiphanova, E I Tolstykh, I Deltour, J Schüz, A V Akleyev
Health effects of in utero exposure to ionizing radiation, especially among adults, are still unclear. The aim of this study was to analyze cancer risk in a cohort of subjects exposed in utero due to releases of nuclear waste into the Techa River in the Southern Urals, taking into account additional postnatal exposure. Analysis for solid cancer was based on 242 cases among 10,482 cohort members, accumulating 381,948 person-years at risk, with follow-up from 1956-2009, while analysis for hematological malignancies was based on 26 cases among 11,070 persons, with 423,502 person-years at risk, with follow-up from 1953-2009...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28692406/mortality-from-circulatory-diseases-and-other-non-cancer-outcomes-among-nuclear-workers-in-france-the-united-kingdom-and-the-united-states-inworks
#16
COMPARATIVE STUDY
Michael Gillies, David B Richardson, Elisabeth Cardis, Robert D Daniels, Jacqueline A O'Hagan, Richard Haylock, Dominique Laurier, Klervi Leuraud, Monika Moissonnier, Mary K Schubauer-Berigan, Isabelle Thierry-Chef, Ausrele Kesminiene
Positive associations between external radiation dose and non-cancer mortality have been found in a number of published studies, primarily of populations exposed to high-dose, high-dose-rate ionizing radiation. The goal of this study was to determine whether external radiation dose was associated with non-cancer mortality in a large pooled cohort of nuclear workers exposed to low-dose radiation accumulated at low dose rates. The cohort comprised 308,297 workers from France, United Kingdom and United States...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28685638/a-review-of-dosimetry-used-in-epidemiological-studies-considered-to-evaluate-the-linear-no-threshold-lnt-dose-response-model-for-radiation-protection
#17
John E Till, Harold L Beck, Helen A Grogan, Emily A Caffrey
BACKGROUND: Accurate dosimetry is key to deriving the dose response from radiation exposure in an epidemiological study. It becomes increasingly important to estimate dose as accurately as possible when evaluating low dose and low dose rate as the calculation of excess relative risk per Gray (ERR/Gy) is very sensitive to the number of excess cancers observed, and this can lead to significant errors if the dosimetry is of poor quality. By including an analysis of the dosimetry, we gain a far better appreciation of the robustness of the work from the standpoint of its value in supporting the shape of the dose response curve at low doses and low dose rates...
July 7, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28676789/importance-of-the-sequence-directed-dna-shape-for-specific-binding-site-recognition-by-the-estrogen-related-receptor
#18
Kareem Mohideen-Abdul, Karima Tazibt, Maxime Bourguet, Isabelle Hazemann, Isabelle Lebars, Maria Takacs, Sarah Cianférani, Bruno P Klaholz, Dino Moras, Isabelle M L Billas
Most nuclear receptors (NRs) bind DNA as dimers, either as hetero- or as homodimers on DNA sequences organized as two half-sites with specific orientation and spacing. The dimerization of NRs on their cognate response elements (REs) involves specific protein-DNA and protein-protein interactions. The estrogen-related receptor (ERR) belongs to the steroid hormone nuclear receptor (SHR) family and shares strong similarity in its DNA-binding domain (DBD) with that of the estrogen receptor (ER). In vitro, ERR binds with high affinity inverted repeat REs with a 3-bps spacing (IR3), but in vivo, it preferentially binds to single half-site REs extended at the 5'-end by 3 bp [estrogen-related response element (ERREs)], thus explaining why ERR was often inferred as a purely monomeric receptor...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28676139/object-decision-and-multiple-sclerosis-a-preliminary-study
#19
N Caputi, A Matrella, Rocco Totaro, C Raparelli, S Pontecorvo, D Di Giacomo, D Passafiume
The aim of this research was to study cognitive dysfunctions in multiple sclerosis (MS) by exploring subtle cognitive tasks, usually not included in the standard neuropsychological assessment. We wished to investigate whether it is possible to identify object decision deficits in MS patients without evident cognitive impairment; secondary objectives were to understand whether these deficits can be detected in the early stages of the disease and whether there are differences related to different phenotypes. Participants were divided into four groups: (a) 12 patients with early relapsing-remitting MS [ERR]; (b) 14 with late relapsing-remitting MS [LRR]; (c) 10 with secondary progressive MS [SP]; (d) 36 healthy controls [HCs]...
April 2017: Functional Neurology
https://www.readbyqxmd.com/read/28675939/homoisoflavanones-with-estrogenic-activity-from-the-rhizomes-of-polygonatum-sibiricum
#20
Hui Chen, Yu-Jie Li, Xiao-Fei Li, Yan-Jun Sun, Hong-Wei Li, Fang-Yi Su, Yan-Gang Cao, Yan-Li Zhang, Xiao-Ke Zheng, Wei-Sheng Feng
A new homoisoflavanone, (3R)-5-hydroxy-7-methoxyl-3-(2'-hydroxy-4'- methoxybenzyl)-chroman-4-one (1), together with six known analogs, were isolated from the rhizomes of Polygonatum sibiricum. Their structures were elucidated on the basis of extensive spectroscopic analysis. All compounds were tested for their estrogenic activity using the MCF-7 estrogenresponsive human breast cancer cell lines. At a dose of 0.1 μmol/L, compounds 1-7 exhibited significant proliferative effects on MCF-7 cells compared with E2...
July 4, 2017: Journal of Asian Natural Products Research
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