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https://www.readbyqxmd.com/read/28646655/syntheses-toxicities-and-anti-inflammation-of-h2s-donors-based-on-non-steroidal-anti-inflammatory-drugs
#1
Meng Li, Jili Li, Taofeng Zhang, Quanyi Zhao, Jie Cheng, Bin Liu, Zhen Wang, Libo Zhao, Chenwei Wang
Three series of H2S donors based on NSAIDs were synthesized and characterized by (1)H-NMR, IR and ESI-HRMS. The H2S-release abilities of all compounds were evaluated in the presence of TECP or cysteine. The results show all compounds were fast H2S-releasers, and their half-lives were in range of 0-20 min. Under the same condition, H2S released from compound 9 was more than any other compounds. In cytotoxicity aspect, all compounds but 1 and 2 displayed much lower toxicities to both LO2 and HepG2 cell lines, and the IC50 values of most compounds were over 800 μM...
June 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646549/inhibition-of-jnk-signaling-mediates-ppar%C3%AE-dependent-protection-against-intrahepatic-cholestasis-by-fenofibrate
#2
Manyun Dai, Julin Yang, Minzhu Xie, Jiao Lin, Min Luo, Huiying Hua, Gangming Xu, Hante Lin, Danjun Song, Yuqing Cheng, Bin Guo, Jinshun Zhao, Frank J Gonzalez, Aiming Liu
BACKGROUND AND PURPOSE: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for the treatment of hyperlipidemia. Although fibrate drugs were reported to be beneficial for cholestasis, the underlying mechanism has not been determined. EXPERIMENTAL APPROACH: Wild-type mice and Pparα-null mice were orally pretreated with fenofibrate for three days, following which ANIT was administered to induce cholestasis. The potent experimental PPARα agonist WY14643 was used to validate the role of PPARα, and the JNK inhibitor SP600125 was employed to explore the role of the JNK pathway in cholestatic liver injury...
June 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28646540/animal-embryotoxicity-studies-of-key-non-artemisinin-antimalarials-and-use-in-women-in-the-first-trimester
#3
REVIEW
Robert L Clark
The World Health Organization currently recommends quinine+clindamycin for use against malaria in the first trimester. This may soon change to recommending artemisinin-based combination therapies (standard duration of dosing = 3 days). The non-artemisinin partner drugs include amodiaquine, lumefantrine, mefloquine, piperaquine, sulfadoxine+pyrimethamine, and pyronaridine. For quinine, clindamycin, and mefloquine and the combinations of sulfadoxine+pyrimethamine and artemether+lumefantrine, there are reports (including studies without internal comparison groups) that combined describe 304 to >1100 exposures of women in the first trimester for each drug with no conclusive evidence of adverse effects on pregnancy at therapeutic doses...
June 24, 2017: Birth defects research
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#4
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28646440/a-comparison-of-three-different-intravitreal-treatment-modalities-of-macular-edema-due-to-branch-retinal-vein-occlusion
#5
Havva Erdogan Kaldırım, Serpil Yazgan
PURPOSE: To compare the efficacy of intravitreal injection of ranibizumab, dexamethasone implant and aflibercept for the management of macular edema (ME) related to branch retinal vein occlusion (BRVO). METHODS: This retrospective and comparative study included 62 eyes of 62 patients with BRVO and ME. Patients received one of the following treatments: 0.5 mg ranibizumab (group 1, n = 22), 0.7 mg dexamethasone implant (group 2, n = 20) and 2 mg aflibercept (group 3, n = 20)...
June 23, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28646347/alendronate-treatment-induces-il-1b-expression-and-apoptosis-in-glioblastoma-cell-line
#6
Paola Maura Tricarico, Angeladine Epate, Fulvio Celsi, Sergio Crovella
Alendronate (ALD), one among the nitrogen-containing bisphosphonates (NBPs), is currently used for the treatment of many pathological conditions. Unfortunately, although generally tolerated, NBPs treatment has been associated with central nervous system (CNS) adverse outcomes, such as amnesia, hallucinations and visual disturbances. So, we analyzed the effect of ALD treatment in glial cells, the main sources of cholesterol for neurons and principal cells involved in the immunological defense of the brain. We treated a glial cell line (U87-MG) with increasing doses of ALD (0...
June 23, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28646254/cytoprotective-effects-of-diallyl-trisulfide-against-valproate-induced-hepatotoxicity-new-anticonvulsant-strategy
#7
Ahmed A Shaaban, Dina S El-Agamy
Sodium valproate (VP) is an important antiepileptic drug, although it can produce deleterious hepatotoxic reactions. Diallyl trisulfide (DATS) is the principle component of garlic oil that possesses antioxidant properties. This study explored the potential hepatoprotective activity of DATS against VP-induced hepatic damage and its underlying mechanisms. In addition, the study assessed the effect of DATS on VP antiepileptic activity. Rats were given DATS once daily at two different doses along with VP for 2 weeks...
June 23, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28646078/stereospecific-metabolism-of-r-and-s-warfarin-by-human-hepatic-cytosolic-reductases
#8
Dustyn A Barnette, Bryce Johnson, Dakota L Pouncey, Robert Nshimiyimana, Linda Desrochers, Thomas E Goodwin, Grover Paul Miller
Coumadin (rac-warfarin) is the most commonly used anticoagulant in the world, yet its clinical use is often challenging due to a narrow therapeutic range and inter-individual variations in response. A critical contributor to the uncertainty is variability in warfarin metabolism, which includes mostly oxidative but also reductive pathways. Reduction of each warfarin enantiomer yields two warfarin alcohol isomers, and the corresponding four alcohols retain varying levels of anticoagulant activity. Studies on the kinetics of warfarin reduction have often lacked resolution of parent drug enantiomers and suffered from co-elution of pairs of alcohol metabolites; thus, those studies fail to establish the importance of individual, stereospecific reductive pathways...
June 23, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28645996/treatment-of-suspected-pulmonary-embolism-in-a-morbidly-obese-patient
#9
Viviene Heitlage, Mary Beth Borgstadt, Lisa Carlson
PURPOSE: A case highlighting challenges with enoxaparin dosage and monitoring in obese patients is presented. SUMMARY: A morbidly obese 22-year-old Caucasian female (height, 168 cm; weight, 322 kg; body mass index [BMI], 114 kg/m(2)) who presented to the emergency department with acute-onset dyspnea and hypoxia was empirically initiated on enoxaparin for suspected pulmonary embolism at the institution's standard maximum dosage (160 mg subcutaneously every 12 hours)...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28645995/mepolizumab-for-the-treatment-of-severe-eosinophilic-asthma
#10
REVIEW
Mara N Poulakos, Shawna M Cargill, Melissa F Waineo, Allen L Wolford
PURPOSE: Published data on the pharmacology, pharmacokinetics and pharmacodynamics, and clinical efficacy and safety of the interleukin-5 antagonist mepolizumab are reviewed. SUMMARY: Asthma of the eosinophilic phenotype is characterized by persistent eosinophilic airway inflammation promoted primarily by T-helper type 2 cytokines, the key regulator of eosinophils. Patients with severe eosinophilic asthma are burdened by the need to administer high doses of corticosteroids to help manage their symptoms...
July 1, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28645857/exploring-the-effect-of-end-binding-proteins-and-microtubule-targeting-chemotherapy-drugs-on-microtubule-dynamic-instability
#11
Diana White, Stéphane Honoré, Florence Hubert
Microtubules (MTs) play a key role in normal cell development and are a primary target for many cancer chemotherapy MT targeting agents (MTAs). As such, understanding MT dynamics in the presence of such agents, as well as other proteins that alter MT dynamics, is extremely important. In general, MTs grow relatively slowly and shorten very fast (almost instantaneously), an event referred to as a catastrophe. These dynamics, referred to as dynamic instability, have been studied in both experimental and theoretical settings...
June 20, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28645838/sensitivity-analysis-and-uncertainty-quantification-in-pulmonary-drug-delivery-of-orally-inhaled-pharmaceuticals
#12
Jun Lu, Jinxiang Xi, Joseph E Langenderfer
In spite of widespread use of modeling tools in inhalation dosimetry, it remains difficult to quantify the output uncertainties when subjected to various sources of input variability. This study aimed to develop a computational model that can quantify the input sensitivity and output uncertainty in pulmonary drug delivery by coupling probabilistic analysis package NESSUS with ANSYS Fluent. An image-based mouth-lung model was used to simulate the transport and deposition of drug particles and variability in particle size, density, and inhalation speed were considered...
June 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28645783/maerua-angolensis-stem-bark-extract-reverses-anxiety-and-related-behaviours-in-zebrafish-involvement-of-gabaergic-and-5-ht-systems
#13
Charles Kwaku Benneh, Robert Peter Biney, Priscilla Kolibea Mante, Augustine Tandoh, Donatus Wewura Adongo, Eric Woode
ETHNOPHARMACOLOGICAL RELEVANCE: Maerua angolensis DC (Capparaceae) has been employed in the management of several central nervous system (CNS) disorders including anxiety. This study evaluated the anxiolytic effects of the petroleum ether/ethyl acetate fraction stem bark extract and its possible mechanism(s) using zebrafish anxiety models. METHODS: Adult zebrafish, tested in the novel tank and light dark tests, have shown by previous authors to be sensitive to the anxiolytic effects of known anxiolytic drugs...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28645776/selective-inhibition-of-flt3-by-gilteritinib-in-relapsed-or-refractory-acute-myeloid-leukaemia-a-multicentre-first-in-human-open-label-phase-1-2-study
#14
Alexander E Perl, Jessica K Altman, Jorge Cortes, Catherine Smith, Mark Litzow, Maria R Baer, David Claxton, Harry P Erba, Stan Gill, Stuart Goldberg, Joseph G Jurcic, Richard A Larson, Chaofeng Liu, Ellen Ritchie, Gary Schiller, Alexander I Spira, Stephen A Strickland, Raoul Tibes, Celalettin Ustun, Eunice S Wang, Robert Stuart, Christoph Röllig, Andreas Neubauer, Giovanni Martinelli, Erkut Bahceci, Mark Levis
BACKGROUND: Internal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia. METHODS: In this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment...
June 20, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28645696/exercise-training-improves-functional-status-in-hypertensive-older-adults-under-angiotensin-converting-enzymes-inhibitors-medication
#15
Liliana C Baptista, Aristides M Machado-Rodrigues, Manuel Teixeira Veríssimo, Raul A Martins
BACKGROUND: The study aims to analyze the effect of three types of treatment on functional status, and cardiovascular risk outcomes in hypertensive older adults with comorbidities. METHODS: Participants (n=418) underwent one of the following 3 conditions: i) multicomponent exercise training 3times/week (MEX; n=116); ii) angiotensin converting enzyme inhibitors used mono-dose daily (ACEi; n=70); iii) combined exercise and ACEi drugs (ACEiMEX; n=232). The trial was completed by 82% of the participants (n=342): MEX (n=90); ACEi (n=66); ACEiMEX (n=186)...
June 20, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28645659/synthesis-in-vitro-and-in-vivo-giardicidal-activity-of-nitrothiazole-nsaid-chimeras-displaying-broad-antiprotozoal-spectrum
#16
Blanca Colín-Lozano, Ismael León-Rivera, Manuel Jesús Chan-Bacab, Benjamín Otto Ortega-Morales, Rosa Moo-Puc, Vanessa López-Guerrero, Emanuel Hernández-Núñez, Raúl Argüello-Garcia, Thomas Scior, Elizabeth Barbosa-Cabrera, Gabriel Navarrete-Vázquez
We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis...
May 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28645191/how-effective-is-algorithm-guided-treatment-for-depressed-inpatients-results-from-the-randomized-controlled-multicenter-german-algorithm-project-3-trial
#17
Mazda Adli, Katja Wiethoff, Thomas C Baghai, Robert Fisher, Florian Seemüller, Gregor Laakmann, Peter Brieger, Joachim Cordes, Jaroslav Malevani, Gerd Laux, Iris Hauth, Hans-Jürgen Möller, Klaus-Thomas Kronmüller, Michael N Smolka, Peter Schlattmann, Maximilian Berger, Roland Ricken, Thomas J Stamm, Andreas Heinz, Michael Bauer
Background: Treatment algorithms are are considered as key to improve outcomes by enhancing the quality of care. This is the first randomized controlled study to evalutate the clinical effect of algorithm-guided treatment in inpatients with major depressive disorder (MDD). Methods: Inpatients, aged 18-70 years with MDD from 10 German psychiatric departments were randomized to 5 different treatment arms (from 2000 to 2005), three of which were standardized stepwise drug treatment algorithms (ALGO)...
June 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28645136/childhood-traumatic-experiences-and-the-association-with-marijuana-and-cocaine-use-in-adolescence-through-adulthood
#18
Joy D Scheidell, Kelly Quinn, Susan P McGorray, B Christopher Frueh, Nisha N Beharie, Linda B Cottler, Maria R Khan
BACKGROUND AND AIMS: Examination of longitudinal relationships between childhood traumatic experiences and drug use across the life-course at the national level, with control of confounding by other forms of trauma, is needed. We aimed to estimate the prevalence of nine typologies of childhood traumas and the cumulative number experienced, correlation between traumas, and associations between individual and cumulative number of traumas with drug use during adolescence, emerging adulthood, and adulthood...
June 23, 2017: Addiction
https://www.readbyqxmd.com/read/28645092/examining-effectiveness-of-tailorable-computer-assisted-therapy-programmes-for-substance-misuse-programme-usage-and-clinical-outcomes-data-from-breaking-free-online
#19
Sarah Elison, Andrew Jones, Jonathan Ward, Glyn Davies, Stephanie Dugdale
RATIONALE: When evaluating complex, tailorable digital behavioural interventions, additional approaches may be required alongside established methodologies such as randomised controlled trials (RCTs). Research evaluating a computer-assisted therapy (CAT) programme for substance misuse, Breaking Free Online (BFO), is informed by Medical Research Council (MRC) guidance recommending examination of 'mechanisms of action' of individual intervention strategies, which is relevant when evaluating digital interventions with content that may evolve over time...
May 23, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28645043/in-vitro-and-in-vivo-behavior-of-dna-tetrahedrons-as-tumor-targeting-nanocarriers-for-doxorubicin-delivery
#20
Ji Hee Kang, Kyoung-Ran Kim, Hyukjin Lee, Dae-Ro Ahn, Young Tag Ko
Deoxyribonucleic acid (DNA) is a versatile material with high applicability and inherent biocompatibility. L-DNA, the perfect mirror form of the naturally occurring D-DNA, has been used in DNA nanotechnology. It has thermodynamically identical properties to D-DNA, is capable of self-assembly and bio-orthogonal base-pairing, and is resistant to nuclease activity. We previously constructed an L-DNA tetrahedron (L-Td) and found that this nanostructure has remarkably higher capacity for cell penetration than its natural counterpart (D-Td)...
June 16, 2017: Colloids and Surfaces. B, Biointerfaces
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