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https://www.readbyqxmd.com/read/28806859/analysis-of-low-molecular-weight-compounds-using-maldi-and-ldi-tof-ms-direct-detection-of-active-pharmaceutical-ingredients-in-different-formulations
#1
João L Bronzel, Cintia D F Milagre, Humberto M S Milagre
Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS) is a high throughput, easy to use analytical technique. The simple sample preparation of this technique and its tolerance to the presence of contaminants are among its advantages. In contrast, depending on the matrix used, MALDI can ionize and generates ions in the low m/z range that complicate the interpretation of the spectra of low molecular weight compounds. To address this issue, one can envisage the use of tunable ionic matrices that can reduce the low m/z interferents...
August 14, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28806782/the-use-of-18f-fluoro-deoxy-glucose-positron-emission-tomography-18f-fdg-pet-as-a-non-invasive-pharmacodynamic-biomarker-to-determine-the-minimally-pharmacologically-active-dose-of-azd8835-a-novel-pi3k%C3%AE-inhibitor
#2
Juliana Maynard, Sally-Ann Emmas, Francois-Xavier Ble, Herve Barjat, Emily Lawrie, Urs Hancox, Urszula M Polanska, Alison Pritchard, Kevin Hudson
BACKGROUND: The phosphatidyl inositol 3 kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) signal transduction pathway is frequently de-regulated and activated in human cancer and is an important therapeutic target. AZD8835 is a PI3K inhibitor, with selectivity against PI3K α and δ isoforms, which is currently in Phase 1 clinical trials. 18F-Fluoro-deoxy-glucose positron emission tomography (18F-FDG PET) is a non-invasive pharmacodynamic imaging biomarker that has become an integral part of drug development...
2017: PloS One
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#3
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28806774/fibroblast-growth-factor-receptor-1-mediates-internalization-of-pathogenic-spotted-fever-rickettsiae-into-host-endothelium
#4
Abha Sahni, Jignesh Patel, Hema P Narra, Casey L C Schroeder, David H Walker, Sanjeev K Sahni
Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28806666/doxorubicin-loaded-environmentally-friendly-carbon-dots-as-a-novel-drug-delivery-system-for-nucleus-targeted-cancer-therapy
#5
Yifang Yuan, Bin Guo, Liying Hao, Na Liu, Yunfeng Lin, Wushuang Guo, Xiaoguang Li, Bin Gu
Chemotherapy is widely applied against various kinds of carcinoma. Generally, chemotherapeutic agents, such as Doxorubicin (DOX), Paclitaxel (PTX), 5-Fluorouracil (5-FU), Methotrexate (MTX), and Vinblastine (VLB) are combined with a view to maximizing their efficacy. Unfortunately, chemotherapeutics are indiscriminate and also kill normal healthy cells, resulting in serious side effects. This non-productive and destructive distribution of chemotherapeutics is regarded as one of the largest problems associated with chemotherapy...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28806653/novel-microemulsion-based-gels-for-topical-delivery-of-indomethacin-formulation-physicochemical-properties-and-in-vitro-drug-release-studies
#6
Anna Froelich, Tomasz Osmałek, Agnieszka Snela, Paweł Kunstman, Barbara Jadach, Marta Olejniczak, Grzegorz Roszak, Wojciech Białas
HYPOTHESIS: Microemulsion-based semisolid systems may be considered as an interesting alternative to the traditional dosage forms applied in topical drug delivery. Mechanical properties of topical products are important both in terms of application and dosage form effectiveness. In this study we designed and evaluated novel microemulsion-based gels with indomethacin and analyzed the factors affecting their mechanical characteristics and drug release. EXPERIMENTS: The impact of the microemulsion composition on the extent of isotropic region was investigated with the use of pseudoternary phase diagrams...
August 4, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28806640/the-importance-of-nutrition-in-aiding-recovery-from-substance-use-disorders-a-review
#7
REVIEW
Kendall D Jeynes, E Leigh Gibson
BACKGROUND: Nutrition is a prerequisite for health; yet, there is no special nutritional assessment or guidance for drug and alcohol dependent individuals, despite the fact that their food consumption is often very limited, risking malnutrition. Further, the premise is examined that malnutrition may promote drug seeking and impede recovery from substance use disorders (SUD). METHOD: A narrative review addressed the relationship between substance use disorders and nutrition, including evidence for malnutrition, as well as their impact on metabolism and appetite regulation...
August 4, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28806372/exploring-rural-disparities-in-medical-diagnoses-among-veterans-with-transgender-related-diagnoses-utilizing-veterans-health-administration-care
#8
Leigh A Bukowski, John Blosnich, Jillian C Shipherd, Michael R Kauth, George R Brown, Adam J Gordon
OBJECTIVES: Research shows transgender individuals experience pronounced health disparities compared with their nontransgender peers. Yet, there remains insufficient research about health differences within transgender populations. This study seeks to fill this gap by exploring how current urban/rural status is associated with lifetime diagnosis of mood disorder, alcohol dependence disorder, illicit drug abuse disorder, tobacco use, posttraumatic stress disorder, human immunodeficiency virus, and suicidal ideation or attempt among veterans with transgender-related diagnoses...
September 2017: Medical Care
https://www.readbyqxmd.com/read/28806055/selective-release-system-for-antioxidative-and-anti-inflammatory-activities-using-h2o2-responsive-therapeutic-nanoparticles
#9
A Young Kim, Ji Hoon Ha, Soo Nam Park
We developed nanoparticles that were degraded by H2O2, a reactive oxygen species (ROS), to study a drug delivery system that targets damaged skin cells with oxidative stress and inflammation. In this study, tyrosol-incorporated copolyoxalate (TPOX) was synthesized by using 1,4-cyclohexanedimethanol, 4-(2-hydroxyethyl)phenol (tyrosol) and oxalyl chloride (Mw ~8835 Da). In vitro drug release behavior was assessed by loading nile red, a lipophilic fluorescent material such as quercetin, into the TPOX nanoparticles...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28806046/electrolytes-sodium-disorders
#10
Michael M Braun, Megan Mahowald
Sodium disorders (ie, hyponatremia, hypernatremia) are common electrolyte disturbances in clinical medicine and are associated with increased rates of morbidity and mortality. Etiologies of hyponatremia are classified into four categories. The first is pseudohyponatremia, in which the sodium level is low due to hyperproteinemia, hyperlipidemia, or hyperglycemia. The other three categories are based on overall patient fluid status and include hypovolemic (commonly due to fluid loss), hypervolemic (commonly due to fluid retention from heart failure, cirrhosis, or renal failure), and euvolemic (most often because of syndrome of inappropriate secretion of antidiuretic hormone)...
August 2017: FP Essentials
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#11
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#12
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28805783/-effect-of-the-cytoflavin-on-the-distal-polyneuropathy-severity-in-patients-with-diabetic-foot-syndrome-with-arteries-mediacalcinosis
#13
V D Skripko, A L Kovalenko, V A Zaplutanov
The aim of the study was to evaluate the effectiveness of cytoflavin in the complex treatment of patients with diabetic foot syndrome. MATERIAL AND METHODS: The research is based on the results of a comprehensive survey of 140 people with diabetic foot syndrome. Depending on the treatment, all patients were divided into 2 groups. The first group (n=35) received basic therapy. The second group (n=35) in addition to basic therapy received cytoflavin 10 ml (+200 ml 0.9% NaCl) for 10 days, followed by switching to the tablet form of the drug 2 tablets twice a day for 1 month...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28805780/-regional-and-peripheral-blockades-for-prevention-of-chronic-post-thoracotomy-pain-syndrome-in-oncosurgical-practice
#14
V E Khoronenko, A S Malanova, D S Baskakov, A B Ryabov, O V Pikin
AIM: To compare an effectiveness of thoracic epidural anesthesia/analgesia, paravertebral and intercostal blockades in prevention of chronic post-thoracotomy pain syndrome (CPTPS) in oncosurgery. MATERIAL AND METHODS: There were 300 patients who underwent open surgery including lobectomy or pneumonectomy. Patients were randomized into 3 groups depending on type of anesthesia: TEA (n=100) - combined general and epidural anesthesia; PVB (n=50) - combined general and paravertebral anesthesia; ICB (n=50) - general anesthesia was supplemented by intercostal blockade after removal of the drug...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28805150/diffracting-addicting-binaries-an-analysis-of-personal-accounts-of-alcohol-and-other-drug-addiction
#15
Kiran Pienaar, David Moore, Suzanne Fraser, Renata Kokanovic, Carla Treloar, Ella Dilkes-Frayne
Associated with social and individual harm, loss of control and destructive behaviour, addiction is widely considered to be a major social problem. Most models of addiction, including the influential disease model, rely on the volition/compulsion binary, conceptualising addiction as a disorder of compulsion. In order to interrogate this prevailing view, this article draws on qualitative data from interviews with people who describe themselves as having an alcohol or other drug 'addiction', 'dependence' or 'habit'...
September 2017: Health (London)
https://www.readbyqxmd.com/read/28805085/strategies-to-release-doxorubicin-from-doxorubicin-delivery-vehicles
#16
Juan Li, Bin Zhang, Chunwen Yue, Jing Wu, Lanxia Zhao, Deqing Sun, Rongmei Wang
Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli...
August 13, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28805013/drug-free-macromolecular-therapeutics-induce-apoptosis-via-calcium-influx-and-mitochondrial-signaling-pathway
#17
Lian Li, Jiyuan Yang, Jiawei Wang, Jindřich Kopeček
Recently, an innovative paradigm has been proposed in macromolecular therapeutics for treatment of B-cell lymphomas that can specifically kill cancer cells without a drug. The design rationale of this drug-free macromolecular therapeutic (DFMT) system is crosslinking the cell surface receptor to initiate apoptosis. However, how the apoptosis signal is triggered after receptor hyper-crosslinking remains to be elucidated. Here, two pathways, calcium influx dependent pathway and mitochondrial signal pathway, are identified to play major roles in triggering the programmed cell death...
August 14, 2017: Macromolecular Bioscience
https://www.readbyqxmd.com/read/28804757/one-aptamer-two-functions-the-full-length-aptamer-inhibits-ampa-receptors-while-the-short-one-inhibits-both-ampa-and-kainate-receptors
#18
William J Jaremko, Zhen Huang, Wei Wen, Andrew Wu, Nicholas Karl, Li Niu
AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the Journal of Biological Chemistry by Jaremko et al. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors...
2017: RNA & Disease
https://www.readbyqxmd.com/read/28804691/combination-of-celecoxib-celebrex-%C3%A2-and-cd19-car-redirected-ctl-immunotherapy-for-the-treatment-of-b-cell-non-hodgkin-s-lymphomas
#19
REVIEW
Tam Nm Dinh, Alexandra S Onea, Ali R Jazirehi
The nonsteroidal anti-inflammatory drug (NSAID) Celecoxib (Celebrex(®)) received Food and Drug Administration (FDA) approval in 1998 for treatment of osteoarthritis and rheumatoid arthritis, and in recent years, its use has been extended to various types of malignancies, such as breast, colon, and urinary cancers. To maintain the survival of malignant B cells, non-Hodgkin's Lymphoma (NHL) is highly dependent on inflammatory microenvironment, and is inhibited by celecoxib. Celecoxib hinders tumor growth interacting with various apoptotic genes, such as cyclooxygenase-2 (Cox-2), B-cell lymphoma 2 (Bcl-2) family, phosphor-inositide-3 kinase/serine-threonine-specific protein kinase (PI3K/Akt), and inhibitors of apoptosis proteins (IAP) family...
2017: American Journal of Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28804615/pharmacological-effects-of-a-synthetic-quinoline-a-hybrid-of-tomoxiprole-and-naproxen-against-acute-pain-and-inflammation-in-mice-a-behavioral-and-docking-study
#20
Hossein Hosseinzadeh, Fatemeh Mazaheri, Razieh Ghodsi
OBJECTIVES: In the present study, we investigated the potential anti-nociceptive activity and acute anti-inflammatory effect of a synthetic quinoline compound (2-(4-Methoxyphenyl)benzo[h]quinoline-4-carboxylic acid, QC), possessing structural elements of both naproxen and tomoxiprole drugs. MATERIALS AND METHODS: The anti-nociceptive activity of QC was evaluated using chemical- and thermal-induced nociception models and its acute anti-inflammatory effect was evaluated by xylene-induced ear edema test in mice...
April 2017: Iranian Journal of Basic Medical Sciences
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