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Dose response

Jamie W Sleigh, Susana Vacas, Alana M Flexman, Pekka O Talke
BACKGROUND: The depth of dexmedetomidine-induced sedation is difficult to assess without arousing the patient. We evaluated frontal electroencephalogram (EEG) as an objective measure of dexmedetomidine-induced sedation. Our aims were to characterize the response patterns of EEG during a wide range of dexmedetomidine-induced sedation and to determine which spectral power best correlated with assessed levels of dexmedetomidine-induced sedation. METHODS: Sedline EEG sensor was positioned on the forehead of 16 volunteers...
June 20, 2018: Anesthesia and Analgesia
Bing Li, Xiaoming Xia, Jinhua Wang, Lusheng Zhu, Jun Wang, Guangchi Wang
As a novel neonicotinoids insecticide, acetamiprid has been widely used worldwide. In this study, a laboratory test was conducted to expose earthworms (Eisenia fetida) to artificial soil spiked with various concentrations of acetamiprid (0, 0.05, 0.10, 0.25 and 0.50 mg/kg of soil) respectively after 7, 14, 21 and 28 d. Reactive oxygen species (ROS) generation, antioxidant enzymes activity including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferases (GST), malondialdehyde (MDA) content, and DNA damage were determined in earthworms...
June 19, 2018: Ecotoxicology and Environmental Safety
Marcos de Lima, Betul Oran, Richard E Champlin, Esperanza B Papadopoulos, Sergio A Giralt, Bart L Scott, Basem M William, Joel Hetzer, Eric Laille, Becky Hubbell, Barry S Skikne, Charles Craddock
BACKGROUND: Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve posttransplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy post-alloSCT. METHODS: Adults with MDS or AML in morphological complete remission at CC-486 initiation (42-84 days post-alloSCT) were included...
June 19, 2018: Biology of Blood and Marrow Transplantation
Vina P Nguyen, Heather Landau, Karen Quillen, Dina Brauneis, Anthony C Shelton, Lisa Mendelson, Hafsa Rahman, J Mark Sloan, Shayna Sarosiek, Vaishali Sanchorawala
High dose melphalan and autologous stem cell transplantation (HDM/SCT) has been used in patients with light chain (AL) amyloidosis for over two decades now with durable responses, prolonged survival, and decreasing treatment related mortality. Historically patients with poorer baseline functional status, advanced age, renal compromise and cardiac involvement have been treated with a risk-adapted modified conditioning dose of melphalan (mHDM) of 100-140 mg/m2 prior to SCT. Due in part to these baseline characteristics, patients receiving mHDM/SCT have had poorer outcomes compared to patients receiving full dose of melphalan at 200 mg/m2 ...
June 19, 2018: Biology of Blood and Marrow Transplantation
Cleide Adriane Signor Tirloni, Rhanany Alan Calloi Palozi, Maysa Isernhagen Schaedler, Aline Aparecida Macedo Marques, Lucas Pires Guarnier, Gabriel Selonke Dos Santos, Emerson Luiz Botelho Lourenço, Lauro Mera de Souza, Arquimedes Gasparotto Junior
ETHNOPHARMACOLOGICAL RELEVANCE: Luehea divaricata Mart. (Malvaceae) is an important medicinal species that is widely used as a diuretic in the Brazilian Pantanal region. An ethanolic supernatant that was obtained from an infusion of leaves of this species (ESLD) was recently shown to exert hypotensive and diuretic activity. Nevertheless, the secondary metabolites that are responsible for this activity and the molecular mechanisms of pharmacological action remain unknown. AIM: We performed a detailed study to identify possible active metabolites that are present in different ESLD fractions and investigated their effects on renal and peripheral arteriolar tone...
June 19, 2018: Journal of Ethnopharmacology
Jimmy W Huh, Ramesh Raghupathi
Pediatric traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality in children. Experimental and clinical studies demonstrate that the developmental age, the type of injury (diffuse vs. focal) and sex may play important roles in the response of the developing brain to a traumatic injury. Advancements in acute neurosurgical interventions and neurocritical care have improved and led to a decrease in mortality rates over the past decades. However, survivors are left with life-long behavioral deficits underscoring the need to better define the cellular mechanisms underlying these functional changes...
June 19, 2018: Neuropharmacology
Louis Anthony Tony Cox
Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3...
June 19, 2018: Toxicology and Applied Pharmacology
Ryan G Price, Smith Apisarnthanarax, Stephanie K Schaub, Matthew J Nyflot, Tobias R Chapman, Manuela Matesan, Hubert J Vesselle, Stephen R Bowen
We report on patient-specific quantitative changes in longitudinal sulfur colloid SPECT/CT as a function of regional radiation dose distributions to normal liver in a cohort of hepatocellular carcinoma patients. Dose-response thresholds and slopes varied with baseline liver function metrics, and extreme values were found in patients with fatal hepatotoxicity. Dose-response modeling of normal liver in individual HCC patients has potential to characterize in vivo radiosensitivity, identify high risk subgroups, and personalize treatment planning dose constraints...
June 19, 2018: International Journal of Radiation Oncology, Biology, Physics
Meredith E Bohannon, Tom E Porter, Emma T Lavoie, Mary Ann Ottinger
The upper Hudson River was contaminated with polychlorinated biphenyls (PCB) Aroclor mixtures from the 1940s until the late 1970s. Several well-established biomarkers, such as induction of hepatic cytochrome P450 monooxygenases, were used to measure exposure to PCBs and similar contaminants in birds. In the present study, Japanese quail eggs were injected with a PCB mixture based upon a congener profile found in spotted sandpiper eggs at the upper Hudson River and subsequently, RNA was extracted from hatchling liver tissue for hybridization to a customized chicken cDNA microarray...
June 22, 2018: Journal of Toxicology and Environmental Health. Part A
Paul G Richardson, Jacob Laubach, Sara Gandolfi, Thierry Facon, Katja Weisel, Peter O'Gorman
In multiple myeloma (MM), maintenance therapy is a longer and less intensive treatment course than initial therapy that is administered after induction to delay disease progression. Maintenance and continuous therapy have been shown to suppress minimal residual disease and deepen and prolong responses, with the goal of improving progression-free survival and overall survival. Areas covered: In this review, we have summarized current clinical trial data on maintenance and continuous therapy in newly-diagnosed MM and relapsed/refractory MM (RRMM), focusing on lenalidomide and bortezomib...
June 22, 2018: Expert Review of Anticancer Therapy
Lin Hou, Yazhen Zheng, Yongchao Wang, Yurong Hu, Jinjin Shi, Qi Liu, Huijuan Zhang, Zhenzhong Zhang
Glucose-responsive insulin delivery systems, which can maintain a stable level of blood glucose, have been proposed as a promising method to treat diabetes. Such systems can reduce potential toxicity and enhance patient compliance compared to traditional therapies. Accordingly, we designed a mesoporous silica nanoparticle (MSN)-based glucose-sensitive and self-regulated drug release system to achieve the goal of long circulation and "touch switch" in vivo. In this system, carboxyphenylboronic acid (CPBA) was first modified on the surface of MSN using amidation reaction...
June 22, 2018: ACS Applied Materials & Interfaces
Stine Ulrik Mikkelsen, Lasse Kjaer, Mads Emil Bjørn, Trine Alma Knudsen, Anders Lindholm Sørensen, Christen Bertel Lykkegaard Andersen, Ole Weis Bjerrum, Nana Brochmann, Daniel El Fassi, Torben A Kruse, Thomas Stauffer Larsen, Hans Torben Mourits-Andersen, Claus Henrik Nielsen, Niels Pallisgaard, Mads Thomassen, Vibe Skov, Hans Carl Hasselbalch
Interferon-α2 reduces elevated blood cell counts and splenomegaly in patients with myeloproliferative neoplasms (MPN) and may restore polyclonal hematopoiesis. Its use is limited by inflammation-mediated toxicity, leading to treatment discontinuation in 10-30% of patients. Ruxolitinib, a potent anti-inflammatory agent, has demonstrated benefit in myelofibrosis (MF) and polycythemia vera (PV) patients. Combination therapy (CT) with these two agents may be more efficacious than monotherapy with either, potentially improving tolerability of interferon-α2 as well...
June 22, 2018: Cancer Medicine
Huan-Feng Zhu, Peng-Wei Yan, Li-Jun Wang, Ya-Tian Liu, Jing Wen, Qian Zhang, Yan-Xin Fan, Yan-Hong Luo
Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation...
June 22, 2018: Journal of Cellular Biochemistry
Chen Tu, Ying Liu, Jing Wei, Lianzhen Li, Kirk G Scheckel, Yongming Luo
In this paper, a highly copper-resistant fungal strain NT-1 was characterized by morphological, physiological, biochemical, and molecular biological techniques. Physiological response to Cu(II) stress, effects of environmental factors on Cu(II) biosorption, as well as mechanisms of Cu(II) biosorption by strain NT-1 were also investigated in this study. The results showed that NT-1 belonged to the genus Gibberella, which exhibited high tolerance to both acidic conditions and Cu(II) contamination in the environment...
June 22, 2018: Environmental Science and Pollution Research International
Jiwook Ryu, Sung Ho Lee, Seok Keun Choi, Young Jin Lim
PURPOSE: This study evaluated the long-term tumor control rate (TCR) and symptomatic outcomes of patients treated with gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). METHODS: Thirty-two patients with TS who underwent GKRS between January 1994 and January 2013 with at least 2 years of follow-up were enrolled in the study. Clinical charts and surgical records were retrospectively reviewed to evaluate factors affecting TCR and symptomatic outcomes...
June 21, 2018: Journal of Neuro-oncology
Yosuke Kito, Nozomu Machida, Sadayuki Kawai, Satoshi Hamauchi, Takahiro Tsushima, Akiko Todaka, Tomoya Yokota, Kentaro Yamazaki, Akira Fukutomi, Yusuke Onozawa, Kunihiro Tsuji, Hisashi Doyama, Yutaka Haraguchi, Koji Nakashima, Kenji Kunieda, Keisei Taku, Keita Mori, Hirofumi Yasui
PURPOSE: Although oxaliplatin 130 mg/m2 every 3 weeks was approved for advanced gastric cancer in Japan, data regarding S-1 plus oxaliplatin 130 mg/m2 (SOX130) are limited in Japanese patients with advanced gastric cancer. We investigated the feasibility and safety of SOX130 in Japanese patients with advanced gastric cancer. METHODS: Patients with unresectable or recurrent gastric adenocarcinoma, no previous chemotherapy, and Eastern Cooperative Oncology Group Performance Status of 0-1 were treated with SOX130...
June 21, 2018: International Journal of Clinical Oncology
Verena Liebers, Benjamin Kendzia, Heike Stubel, Gerda Borowitzki, Vitali Gering, Christian Monsé, Olaf Hagemeyer, Rolf Merget, Thomas Brüning, Monika Raulf
The whole-blood assay (WBA) with human fresh blood may provide insight into the features of an individual's innate immunity. To assess this, ex vivo cytokine release is measured after stimulation of whole blood with various stimuli, for instance, endotoxin in vitro. The aim of the present study was to evaluate WBA reproducibility with fresh blood using different calculation models. The blood was collected from 16 healthy volunteers on 6 different days. Ex vivo stimulation was performed in each individual's blood sample for 22 h, using different endotoxin concentrations...
June 22, 2018: Advances in Experimental Medicine and Biology
Garry G Graham, Sophie L Stocker, Diluk R W Kannangara, Richard O Day
PURPOSE OF REVIEW: To review the extent of treatment success or failure with the xanthine oxidoreductase inhibitors allopurinol and febuxostat and indicate how the dosage of urate-lowering therapy (ULT) may be modified to increase the response in the majority of patients with gout. RECENT FINDINGS: Gout flares are associated with serum concentrations of urate above 0.42 mmol/L (7 mg/dL). Achieving and maintaining serum urate below 0.36 mmol/L is considered an effective response to ULT...
June 21, 2018: Current Rheumatology Reports
Jie Tao, Feng Jiang, Cheng Liu, Zhirui Liu, Yudan Zhu, Jian Xu, Yiqin Ge, Kan Xu, Peihao Yin
Chan-su (toad venom) has been used as an analgesic agent in China from ancient to modern times. Bufalin, a non-peptide toxin extracted from toad venom, is considered as one of the analgesic components. The molecular mechanism underlying the anti-nociceptive effects of bufalin remains unclear so far. In this study, we investigated the pharmacological effects of bufalin on pain-related ion channels as well as animal models through patch clamping, calcium imaging and animal behavior observation. Using the whole-cell recording, bufalin caused remarkable suppressive effect on the peak currents of Nav channels (voltage gated sodium channels, VGSCs) of dorsal root ganglion neuroblastomas (ND7-23 cell) in a dose-dependent manner...
June 21, 2018: Molecular Biology Reports
Mark Agulnik, Steven Attia
Sarcomas encompass a group of rare solid tumors responsible for approximately 1% of all cancer-related deaths in the United States each year. Subtypes include, but are not limited to, soft tissue sarcomas (STS) such as leiomyosarcoma, liposarcoma, pleomorphic sarcoma, and gastrointestinal stromal tumor (GIST). Treatment options for patients with STS vary depending on, among other factors, histological subtype. Data from a mix of phase 2 and phase 3 trials have suggested that the orally available multikinase inhibitor regorafenib may have efficacy in patients with STS who have progressed on previous lines of systemic therapy...
June 21, 2018: Targeted Oncology
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