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Negiin Pourafshar, Ashkan Karimi, Xuerong Wen, Eric Sobel, Shirin Pourafshar, Nikhil Agrawal, Emma Segal, Rajesh Mohandas, Mark S Segal
Background: Monitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA. Methods: A total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study...
March 13, 2018: Nephrology, Dialysis, Transplantation
Huanhuan Hu, Naoko Sasaki, Takayuki Ogasawara, Satsue Nagahama, Shamima Akter, Keisuke Kuwahara, Takeshi Kochi, Masafumi Eguchi, Ikuko Kashino, Taizo Murakami, Makiko Shimizu, Akihiko Uehara, Makoto Yamamoto, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Ai Hori, Chihiro Nishiura, Hiroko Okazaki, Teppei Imai, Akiko Nishihara, Toshiaki Miyamoto, Kentaro Tomita, Isamu Kabe, Tetsuya Mizoue, Naoki Kunugita, Seitaro Dohi
Introduction: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. Methods: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss...
March 14, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
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
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
Ariana Sherdil, Stéphan Chabardès, Isabelle Guillemain, Sandrine Michallat, Shivadatta Prabhu, Karine Pernet-Gallay, Olivier David, Brigitte Piallat
PURPOSE: Our objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. METHODS: Five macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12-27 experiments with a mean cumulative dose of 162644 ± 70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days...
March 9, 2018: Epilepsy Research
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
Carolina de la Guardia, David E Stephens, Hang T Dang, Mario Quijada, Oleg V Larionov, Ricardo Lleonart
Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range...
March 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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
Stephan Petersenn
Secondary adrenal insufficiency may pose specific challenges during pregnancy. The interpretation of diagnostic tests is hindered by physiological adaptations of the HPA axis. Due the relevant increases in CBG, measurement of salivary cortisol may be preferable, but lacks sufficiently established cut-offs both for early-morning evaluation and during dynamic testing. Hydrocortisone should be used for replacement to avoid overexposure of the fetus, with dose adjustments according to clinical judgement. To account for increased free cortisol levels during the course of pregnancy, hydrocortisone may be increased by 5-7...
March 15, 2018: Minerva Endocrinologica
Md Moniruzzaman, Young-Won Chin, Jungsook Cho
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells...
March 15, 2018: Cell Stress & Chaperones
Ekwu M Ameh, Sean Tyrrel, Jim Harris, Athanasios Ignatiou, Elena Orlova, Andreas Nocker
Disinfection aims at maximal inactivation of target organisms and the sustainable suppression of their regrowth. Whereas many disinfection efforts achieve efficient inactivation when the effect is measured directly after treatment, there are questions about the sustainability of this effect. One aspect is that the treated bacteria might recover and regain the ability to grow. In an environmental context, another question is how amenable surviving bacteria are to predation by omnipresent bacteriophages. Provisional data suggested that bacteria when subjected to sublethal heat stress might develop a phage-resistant phenotype...
March 15, 2018: Folia Microbiologica
Salvatore Grisanti, Deborah Cosentini, Valeria Tovazzi, Susanna Bianchi, Barbara Lazzari, Francesca Consoli, Elisa Roca, Alfredo Berruti, Vittorio D Ferrari
PURPOSE: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. METHODS: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment...
March 15, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Sylvain Bart, Sacha Roudine, Joël Amossé, Christian Mougin, Alexandre R R Péry, Céline Pelosi
The risk assessment of pesticides on soil fauna is an issue to protect agroecosystem sustainability. Enchytraeids are recognized as relevant soil bioindicators of chemical stress in agroecosystems. In laboratory, the reproduction test was found to be sensitive to reveal chemical impacts on enchytraeids. However, it does not allow to assess the impacts on ecological functions in which enchytraeids are involved. The objectives of this study were (i) to explore the feasibility of the bait-lamina test with enchytraeids under laboratory conditions and (ii) to compare its sensitivity with the Enchytraeid Reproduction Test...
March 15, 2018: Environmental Science and Pollution Research International
Carolina Ribeiro, Rosa Quinta, Ana Raposo, Ana Valentim, José Albuquerque, Manuela Grazina
Objective: Prospective observational study to analyze CYP2D6 pharmacogenetics in 55 Portuguese adult parturients undergoing elective cesarean section and to investigate the association between CYP2D6 alleles and pain score. Methods: DNA was extracted from peripheral blood by standard methods. Genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number determination with TaqMan probes by real-time polymerase chain reaction (PCR)...
March 12, 2018: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Anna Szewczyk, Julie Gehl, Malgorzata Daczewska, Jolanta Saczko, Stine Krog Frandsen, Julita Kulbacka
Calcium electroporation (CaEP) describes the use of electric pulses (electroporation) to transiently permeabilize cells to allow supraphysiological doses of calcium to enter the cytosol. Calcium electroporation has successfully been investigated for treatment of cutaneous metastases in a clinical study. This preclinical study explores the possible use of calcium electroporation for treatment of sarcoma. A normal murine muscle cell line (C2C12), and a human rhabdomyosarcoma cell line (RD) were used in the undifferentiated and differentiated state...
February 20, 2018: Oncotarget
Shengye Liu, Long Zhou, Liyu Yang, Shuai Mu, Tao Fang, Qin Fu
Background: Prolonged and over-dosed administration of glucocorticoids results in more bone remodeling, leading to glucocorticoid-induced osteoporosis, which is primarily due to dysfunction and apoptosis of osteoblasts. The present study investigated the therapeutic effect and molecular mechanism of gastrodin, a natural bioactive compound isolated from the traditional Chinese herbal agent Gastrodia elata, on osteoblastic cells in vivo and in vitro . Materials and Methods: The anti-dexamethasone (DEX) effects of gastrodin on primary osteoblasts were measured by cell viability, flow cytometry, and western blot analysis in vitro , and also extensively examined in a rat model in vivo ...
February 20, 2018: Oncotarget
Evangelos G Papanikolaou, Hakan Yarali, Evi Timotheou, Michael Grynberg, Odysseas Zafeiratis, Herman Tournaye, Robert Najdecki
Introduction: A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017. Materials and methods: The efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients...
2018: Frontiers in Endocrinology
Jorge C Kattah
Background: Previous series of bilateral vestibular loss (BVL) identified numerous etiologies, but surprisingly, a cause in a significant number of cases remains unknown. In an effort to understand possible etiology and management strategies, a global effort is currently in progress. Here, I contribute my 10-year experience with both acute and chronic BVL during the 2007-2017 decade. Methods: This is a retrospective review of the charts and EMR of patients diagnosed with BVL in the last 10 years...
2018: Frontiers in Neurology
Kimberly R Kalli, Matthew S Block, Pashtoon M Kasi, Courtney L Erskine, Timothy J Hobday, Allan Dietz, Douglas Padley, Michael P Gustafson, Barath Shreeder, Danell Puglisi-Knutson, Daniel W Visscher, Toni Kay Mangskau, Glynn Wilson, Keith L Knutson
PURPOSE: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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