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https://www.readbyqxmd.com/read/28213850/gamma-hydroxybutyrate-ghb-content-in-hair-samples-correlates-negatively-with-age-in-succinic-semialdehyde-dehydrogenase-deficiency
#1
S S Johansen, X Wang, D Sejer Pedersen, P L Pearl, J-B Roullet, G R Ainslie, K R Vogel, K M Gibson
Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD...
February 18, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#2
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212944/acute-and-long-term-effects-of-adolescent-methylphenidate-on-decision-making-and-dopamine-receptor-mrna-expression-in-the-orbitofrontal-cortex
#3
Leslie R Amodeo, Eliza Jacobs-Brichford, Matthew S McMurray, Jamie D Roitman
Though commonly used as a treatment for ADHD, the psychostimulant methylphenidate (MPH) is also misused and abused in adolescence in both clinical and general populations. Although MPH acts via pathways activated by other drugs of abuse, the short- and long-term effects of MPH on reward processing in learning and decision-making are not clearly understood. We examined the effect of adolescent MPH treatment on a battery of reward-directed behaviors both in adolescence during its administration and in adulthood after its discontinuation...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212668/association-of-community-sanitation-usage-with-soil-transmitted-helminth-infections-among-school-aged-children-in-amhara-region-ethiopia
#4
William E Oswald, Aisha E P Stewart, Michael R Kramer, Tekola Endeshaw, Mulat Zerihun, Berhanu Melak, Eshetu Sata, Demelash Gessese, Tesfaye Teferi, Zerihun Tadesse, Birhan Guadie, Jonathan D King, Paul M Emerson, Elizabeth K Callahan, Matthew C Freeman, W Dana Flanders, Thomas F Clasen, Christine L Moe
BACKGROUND: Globally, in 2010, approximately 1.5 billion people were infected with at least one species of soil-transmitted helminth (STH), Ascaris lumbricoides, Trichuris trichiura, hookworm (Ancylostoma duodenale and Necator americanus). Infection occurs through ingestion or contact (hookworm) with eggs or larvae in the environment from fecal contamination. To control these infections, the World Health Organization recommends periodic mass treatment of at-risk populations with deworming drugs...
February 17, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#5
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
February 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28211296/recommendations-for-the-medical-management-of-chronic-venous-disease-the-role-of-micronized-purified-flavanoid-fraction-mpff
#6
Ronald Bush, Anthony Comerota, Mark Meissner, Joseph D Raffetto, Steven R Hahn, Katherine Freeman
Scope A systematic review of the clinical literature concerning medical management of chronic venous disease with the venoactive therapy Micronized Purified Flavonoid Fraction was conducted in addition to an investigation of the hemodynamics and mechanism of chronic venous disease. Methods The systematic review of the literature focused on the use of Micronized Purified Flavonoid Fraction (diosmin) which has recently become available in the US, in the management of chronic venous disease. The primary goal was to assess the level of evidence of the role of Micronized Purified Flavonoid Fraction in the healing of ulcers, and secondarily on the improvement of the symptoms of chronic venous disease such as edema...
April 2017: Phlebology
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#7
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28207929/optimisation-of-intestinal-microsomal-preparation-in-the-rat-a-systematic-approach-to-assess-the-influence-of-various-methodologies-on-metabolic-activity-and-scaling-factors
#8
Oliver J D Hatley, Christopher R Jones, Aleksandra Galetin, Amin Rostami-Hodjegan
The metabolic capacity of the intestine and its importance as the initial barrier to systemic exposure can lead to under-estimation of first-pass, and thus overestimation of oral bioavailability. However, the in vitro tools informing estimates of in vivo intestinal metabolism are limited by the complexity of the in vitro matrix preparation and uncertainty with the scaling factors for in vitro to in vivo extrapolation. A number of methods currently exist in the literature for the preparation of intestinal microsomes; however, the impact of key steps in the preparation procedure has not been critically assessed...
February 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28205616/dependence-on-glycolysis-sensitizes-braf-mutated-melanomas-for-increased-response-to-targeted-braf-inhibition
#9
Keisha N Hardeman, Chengwei Peng, Bishal B Paudel, Christian T Meyer, Thong Luong, Darren R Tyson, Jamey D Young, Vito Quaranta, Joshua P Fessel
Dysregulated metabolism can broadly affect therapy resistance by influencing compensatory signaling and expanding proliferation. Given many BRAF-mutated melanoma patients experience disease progression with targeted BRAF inhibitors, we hypothesized therapeutic response is related to tumor metabolic phenotype, and that altering tumor metabolism could change therapeutic outcome. We demonstrated the proliferative kinetics of BRAF-mutated melanoma cells treated with the BRAF inhibitor PLX4720 fall along a spectrum of sensitivity, providing a model system to study the interplay of metabolism and drug sensitivity...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#10
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28202762/maternal-binding-and-neutralizing-igg-responses-targeting-the-c-terminal-region-of-the-v3-loop-are-predictive-of-reduced-peripartum-hiv-1-transmission-risk
#11
David R Martinez, Nathan Vandergrift, Ayooluwa O Douglas, Erin McGuire, John Bainbridge, Nathan I Nicely, David C Montefiori, Georgia D Tomaras, Genevieve G Fouda, Sallie R Permar
The development of an effective maternal HIV-1 vaccine that could synergize with antiretroviral therapy (ART) to eliminate pediatric HIV-1 infection will require the characterization of maternal immune responses capable of blocking transmission of autologous HIV viruses to the infant. We previously identified that maternal plasma antibody binding to linear epitopes within the variable loop 3 (V3) region of HIV envelope (Env) and neutralizing responses against easy to neutralize tier 1 viruses were associated with reduced risk of peripartum HIV infection in the historic U...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#12
REVIEW
L Oni, D B Hawcutt, M A Turner, M W Beresford, S McWilliam, C Barton, B K Park, P Murray, B Wilm, I Copple, R Floyd, M Peak, A Sharma, D J Antoine
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28201962/preparation-and-optimization-of-fast-dissolving-film-of-naratriptan-hydrochloride
#13
Krishna D Koradia, Pradip T Sidhdhapara, Navin R Sheth
BACKGROUND AND OBJECTIVE: Naratriptan is second-generation triptan class of antimigraine drug which selectively bind with 5-HT(1B/1D) receptor. It is widely used to treat the migraine attack due to its better tolerability and lower recurrence rate as compared to other triptans. Despite of the applicability, Naratriptan also have several drawback like slow onset of action and fist pass metabolism which reduce its efficacy. In order to increase the efficacy of naratriptan fast dissolving film is prepared...
February 12, 2017: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/28199939/sorption-and-desorption-of-selected-non-steroidal-anti-inflammatory-drugs-in-an-agricultural-loam-textured-soil
#14
Y Zhang, G W Price, R Jamieson, D Burton, K Khosravi
Non-steroidal, anti-inflammatory drugs (NSAIDs) are widely used pharmaceutical products with analgesic and anti-inflammatory effects that are consistently detected in municipal wastewater systems and in municipal biosolids. Land application of biosolids and irrigation with reclaimed wastewater introduces these compounds into agricultural environments, which is an emerging issue of concern for ecosystem health. In this study, the sorption-desorption behaviour of four commonly consumed NSAIDs, including naproxen (NPX), ibuprofen (IBU), ketoprofen (KTF), and diclofenac (DCF), was examined in a loam textured soil exposed to either an individual-compound or a mixture of the four NSAIDs...
February 6, 2017: Chemosphere
https://www.readbyqxmd.com/read/28199520/implications-of-failure-to-routinely-diagnose-resistance-to-second-line-drugs-in-patients-with-rifampicin-resistant-tuberculosis-on-xpert-mtb-rif-a-multisite-observational-study
#15
Karen R Jacobson, Marinus Barnard, Mary B Kleinman, Elizabeth M Streicher, Elizabeth J Ragan, Laura F White, Ofer Shapira, Tania Dolby, John Simpson, Lesley Scott, Wendy Stevens, Paul D van Helden, Annelies Van Rie, Robin M Warren
No abstract text is available yet for this article.
February 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28198563/frequency-and-predictors-of-analgesic-prescribing-in-u-s-nursing-home-residents-with-persistent-pain
#16
Kevin M Fain, G Caleb Alexander, David D Dore, Jodi B Segal, Andrew R Zullo, Carlos Castillo-Salgado
OBJECTIVES: To quantify prescription analgesic use of elderly nursing home (NH) residents with persistent noncancer pain and to identify individual and facility traits associated with no treatment. DESIGN: Cross-sectional study. SETTING: Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. PARTICIPANTS: Individuals aged 65 and older with persistent noncancer pain were identified from a cross-section of all long-stay U...
February 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28197557/doubly-charged-trimeric-cluster-ions-effective-in-mutual-chiral-recognition-of-tadalafil-and-three-proton-pump-inhibitors
#17
Lu Wang, Yunfeng Chai, Wenquan Zhu, Yuanjiang Pan, Cuirong Sun, Su Zeng
Mutual chiral recognition of four stereoisomers of tadalafil and three pairs of enantiomers of proton pump inhibitors (PPIs) including pantoprazole, lansoprazole, and omeprazole, as well as quantitative analysis of enantiomeric excess is achieved on the basis of the competitive fragmentation of doubly charged trimeric Ni(II) cluster ions. Compared with a singly charged trimeric cluster ion, a doubly charged trimeric cluster ion was proved efficient in the recognition of chiral drugs with one or multiple chiral centers, due to its rich fragmentation ions...
February 15, 2017: Analyst
https://www.readbyqxmd.com/read/28196724/persistence-and-adherence-with-mirabegron-versus-antimuscarinic-agents-in-patients-with-overactive-bladder-a-retrospective-observational-study-in-uk-clinical-practice
#18
Christopher R Chapple, Jameel Nazir, Zalmai Hakimi, Sally Bowditch, Francis Fatoye, Florent Guelfucci, Amine Khemiri, Emad Siddiqui, Adrian Wagg
BACKGROUND: Persistence with antimuscarinic therapy in overactive bladder (OAB) is poor, but may be different for mirabegron, a β3-adrenoceptor agonist with a different adverse event profile. OBJECTIVE: To compare persistence and adherence with mirabegron versus tolterodine extended release (ER) and other antimuscarinics in routine clinical practice over a 12-mo period. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, longitudinal, observational study of anonymised data from the UK Clinical Practice Research Datalink GOLD database...
February 11, 2017: European Urology
https://www.readbyqxmd.com/read/28196335/paternal-nicotine-exposure-alters-hepatic-xenobiotic-metabolism-in-offspring
#19
Markus P Vallaster, Shweta Kukreja, Xinyang Y Bing, Jennifer Ngolab, Rubing Zhao-Shea, Paul D Gardner, Andrew R Tapper, Oliver J Rando
Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal 'quality of life'. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring...
February 14, 2017: ELife
https://www.readbyqxmd.com/read/28195646/ns1209-spd-502-a-novel-selective-ampa-antagonist-for-stroke-neuropathic-pain-or-epilepsy-drug-development-lessons-learned
#20
Jan M Keppel Hesselink
Preclinical Research The selective AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor antagonist, NS1209 (also known as SPD 502) has been explored in several research and development campaigns since its selection as a lead drug candidate in the early 1990s by the Danish biotechnology company, NeuroSearch. The compound was successively tested in animal models of stroke, neuropathic pain and epilepsy. The preclinical data to support development for the treatment of stroke were incomplete, as the compound was administered after the stroke episode, and did not protect subcortical areas of the brain...
February 13, 2017: Drug Development Research
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