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https://www.readbyqxmd.com/read/28343293/pharmacokinetic-and-pharmacodynamic-considerations-in-the-treatment-of-chronic-lymphocytic-leukemia-ibrutinib-idelalisib-and-venetoclax
#1
REVIEW
Madeline Waldron, Allison Winter, Brian T Hill
Management of chronic lymphocytic leukemia has changed markedly over the last several years with the emergence of several novel oral agents targeting B-cell receptor and Bcl-2 signaling pathways. For patients requiring treatment, ibrutinib, idelalisib, and venetoclax offer unique clinical benefits with a different set of therapeutic considerations compared with traditional parenteral therapy. Despite the conveniences afforded by oral therapy, these agents also carry unique logistical obstacles. Drug interactions with agents that are metabolized via the cytochrome P450 3A4 pathway are possible with all three agents...
March 25, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28343167/the-unappreciated-roles-of-the-cholecystokinin-receptor-cck-1-in-brain-functioning
#2
Santiago Ballaz
The CCK(1) receptor is a G-protein-coupled receptor activated by the sulfated forms of cholecystokinin (CCK), a gastrin-like peptide released in the gastrointestinal tract and mammal brain. A substantial body of research supports the hypothesis that CCK(1)r stimulates gallbladder contraction and pancreatic secretion in the gut, as well as satiety in brain. However, this receptor may also fulfill relevant roles in behavior, thanks to its widespread distribution in the brain. The strategic location of CCK(1)r in mesolimbic structures and specific hypothalamic and brainstem nuclei lead to complex interactions with neurotransmitters like dopamine, serotonin, and glutamate, as well as hypothalamic hormones and neuropeptides...
March 25, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28343134/exfoliated-graphene-nanosheets-ph-sensitive-drug-carrier-and-anti-cancer-activity
#3
Nisha Tyagi, Nour F Attia, Kurt E Geckeler
A straightforward and facile method for the exfoliation of graphene sheets using poly(vinylpyrrolidone) nanoparticles of an average size of 42nm was developed and their dual role as pH-sensitive drug carrier and anti-cancer agent was evaluated. The cytotoxic impact of the exfoliated nanosheets (GRP-PVP-NP) was examined on various cells (HCT-116, HeLa, SCC-9, NIH-3T3 and HEK-293cells) by a series of assays. Their cytotoxic nature was attributed to affecting the mitochondrial enzyme activity, proliferation capability, and the formation of tight junctions in cancer cells...
March 16, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28343130/computational-study-of-ibuprofen-removal-from-water-by-adsorption-in-realistic-activated-carbons
#4
Daniel Bahamon, Leticia Carro, Sonia Guri, Lourdes F Vega
Molecular simulations using the Grand Canonical Monte Carlo (GCMC) method have been performed in order to obtain physical insights on how the interaction between ibuprofen (IBP) and activated carbons (ACs) in aqueous mixtures affects IBP removal from water by ACs. A nanoporous carbon model based on units of polyaromatic molecules with different number of rings, defects and polar-oxygenated sites is described. Individual effects of factors such as porous features and chemical heterogeneities in the adsorbents are investigated and quantified...
March 18, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28343018/cus-as-a-gatekeeper-of-mesoporous-upconversion-nanoparticles-based-drug-controlled-release-system-for-tumor-targeted-multimodal-imaging-and-synergetic-chemo-thermotherapy
#5
Xiangjie Su, Feifei Zhao, Yuhui Wang, Xiaosa Yan, Shaona Jia, Bin Du
In this work, a tumor-targeted multifunctional mesoporous upconversion nanoparticle-based drug controlled release system was developed for UCL/MRI/PAT guided synergetic chemo- thermotherapy. Herein, the core-shell mesoporous upconversion nanoparticles served as drug carrier exhibiting higher upconversion luminescence emission intensity, with CuS as a gatekeeper through a cleavable disulfide bond under the influence of glutathione. CuS could not only prevent drug from early release during the delivery but also improve the delivery system function with the ability of photothermal therapy and photoacoustic tomography...
March 22, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28342897/dose-response-effect-of-acute-phencyclidine-on-functional-connectivity-and-dopamine-levels-and-their-association-with-schizophrenia-like-symptom-classes-in-rat
#6
Jaakko Paasonen, Raimo A Salo, Jouni Ihalainen, Juuso V Leikas, Katja Savolainen, Marko Lehtonen, Markus M Forsberg, Olli Gröhn
Current drug treatments for schizophrenia (SCZ) can alleviate positive symptoms, but have little effect on the negative symptoms and cognitive deficits that are difficult to translate into preclinical models for drug development. Therefore, we aimed to determine the dose-response effects of acute phencyclidine (PCP, 1.0-5.0 mg/kg) on rat brain connectivity and detect markers for different SCZ-like symptoms. Pharmacological functional magnetic resonance imaging (phMRI) and microdialysis were used to investigate PCP-induced effects on functional connectivity (FC) and dopamine levels, respectively...
March 22, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28342858/aqueous-extract-from-leaf-of-artocarpus-altilis-provides-cardio-protection-from-isoproterenol-induced-myocardial-damage-in-rats-negative-chronotropic-and-inotropic-effects
#7
Chukwuemeka Nwokocha, Javier Palacios, Mario J Simirgiotis, Jemesha Thomas, Magdalene Nwokocha, Lauriann Young, Rory Thompson, Fredi Cifuentes, Adrian Paredes, Rupika Delgoda
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats. MATERIAL AND METHODS: Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-hour period...
March 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28342789/enhanced-gastric-stability-of-esomeprazole-by-molecular-interaction-and-modulation-of-microenvironmental-ph-with-alkalizers-in-solid-dispersion
#8
Hien Van Nguyen, Namhyun Baek, Beom-Jin Lee
Due to the instability of esomeprazole magnesium dihydrate (EPM), a proton pump inhibitor, in gastric fluid, enteric-coated dosage form is commonly used for therapeutic application. In this study, we prepared new gastric fluid resistant solid dispersions (SDs) containing alkalizers. Then, new mechanistic evidence regarding the effects of pharmaceutical alkalizers on the aqueous stability of EPM in simulated gastric fluid was investigated. The alkalizer-loaded SD were prepared by dissolving or dispersing EPM, hydroxypropyl methylcellulose (HPMC) 6 cps, and an alkalizer, in ethanol 50% (v/v) followed by spray drying...
March 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28342788/analytical-ultracentrifugation-for-analysis-of-doxorubicin-loaded-liposomes
#9
Dora Mehn, Patrizia Iavicoli, Noelia Cabaleiro, Sven Even Borgos, Fanny Caputo, Otmar Geiss, Luigi Calzolai, François Rossi, Douglas Gilliland
Analytical ultracentrifugation (AUC) is a powerful tool for the study of particle size distributions and interactions with high accuracy and resolution. In this work, we show how the analysis of sedimentation velocity data from the AUC can be used to characterize nanocarrier drug delivery systems used in nanomedicine. Nanocarrier size distribution and the ratio of free versus nanoparticle-encapsulated drug in a commercially available liposomal doxorubicin formulation are determined using interference and absorbance based AUC measurements and compared with results generated with conventional techniques...
March 22, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28342786/pharmaceutical-solvates-hydrates-and-amorphous-forms
#10
REVIEW
Anne Marie Healy, Zelalem Ayenew Worku, Dinesh Kumar, Atif M Madi
Active pharmaceutical ingredients (APIs) may exist in various solid forms, which can lead to differences in the intermolecular interactions, affecting the internal energy and enthalpy, and the degree of disorder, affecting the entropy. Differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs and excipients. Hence, solid forms of APIs play a vital role in drug discovery and development in the context of optimization of bioavailability, filing intellectual property rights and developing suitable manufacturing methods...
March 22, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28342783/effect-of-storage-on-the-physical-stability-of-thin-polymethacrylate-perphenazine-films
#11
Kristiina Korhonen, Elina Smolander, Ossi Korhonen, Jarkko Ketolainen, Riikka Laitinen
We evaluated the physical stability of thin polymethacrylate-drug films under three different storage conditions by X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, polarized light microscopy, and Fourier transform infrared spectroscopy. Mechanical properties i.e. elongation, mechanical strength, and in vitro drug release from the thin films were also determined during storage. The films consisted of ammonium methacrylate copolymer (RLPO)/dimethylaminoethyl methacrylate copolymer (EPO), polyvinylpyrroline (PVP)/polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus) and perphenazine (PPZ)...
March 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28342710/emerging-role-of-chemoprotective-agents-in-the-dynamic-shaping-of-plasma-membrane-organization
#12
REVIEW
Natividad R Fuentes, Michael L Salinas, Eunjoo Kim, Robert S Chapkin
In the context of an organism, epithelial cells by nature are designed to be the defining barrier between self and the outside world. This is especially true for the epithelial cells that form the lining of the digestive tract, which absorb nutrients and serve as a barrier against harmful substances. These cells are constantly bathed by a complex mixture of endogenous (bile acids, mucus, microbial metabolites) and exogenous (food, nutrients, drugs) bioactive compounds. From a cell biology perspective, this type of exposure would directly impact the plasma membrane, which consists of a myriad of complex lipids and proteins...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342627/applicability-of-calf-subcutaneous-tissue-to-subcutaneous-injection-in-young-adults
#13
Serap Torun, Şükriye Deniz Mutluay
AIM: The aim of the study is to provide usage of subcutaneous tissue of lateral calf area (region of M. Gastrocnemius) in addition to the existing injection regions and to compare tissue thicknesses of the lateral upper arm, anterior and lateral thigh, anterior abdomen regions and calf regions. BACKGROUND: Subcutaneous injection (SC) is an application of 0.5cc drug with an injection (No. 25 and 8-15-18mm long) to the connective tissue under the skin. Individuals to which SC injection is frequently applied, should rotate the injection areas...
April 2017: Applied Nursing Research: ANR
https://www.readbyqxmd.com/read/28342583/affinity-chromatographic-methodologies-based-on-immobilized-voltage-dependent-anion-channel-isoform-1-and-application-in-protein-ligand-interaction-analysis-and-bioactive-compounds-screening-from-traditional-medicine
#14
Qian Li, Pan Qiao, Xiu Chen, Jing Wang, Liujiao Bian, Xiaohui Zheng
Voltage dependent anion channel isoform 1 (VDAC-1) serves as an attractive target of anti-cancer drugs by mediating the entry and exit of metabolites between cytoplasm and mitochondria. This work reports on the preparation of a VDAC-1-based bioaffinity chromatographic stationary phase by linking the protein on lecithin modified microspheres. An assay of chromatographic methods including frontal analysis, zonal elution, injection dependent analysis and nonlinear chromatography were utilized to investigate the bindings of ATP, NADH and NADPH to VDAC-1...
March 18, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28342366/discovery-of-new-dual-ppar%C3%AE-gpr40-agonists-with-robust-antidiabetic-activity-design-synthesis-and-in-combo-drug-evaluation
#15
Sergio Hidalgo-Figueroa, Gabriel Navarrete-Vázquez, Samuel Estrada-Soto, Diana Giles-Rivas, Francisco J Alarcón-Aguilar, Ismael León-Rivera, Abraham Giacoman-Martínez, Elizabeth Miranda Pérez, Julio C Almanza-Pérez
The design of compounds 1 and 2 was based on the similar scaffold of pharmacophoric groups for PPARγ and GPR40 agonists. In order to find new compounds with improved biological activity, the current manuscript describes a new dual PPARγ-GPR40 agonist. We synthesized two compounds, which were prepared following a multistep synthetic route, and the relative mRNA expression levels of PPARγ, GLUT4, and GPR40 were quantified in cell culture, as well as insulin secretion and [Ca(2+)] intracellular levels. Compound 1 showed a 7-times increase in the mRNA expression of PPARγ, which in turn enhanced the expression levels of GLUT4 respect to control and pioglitazone...
March 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#16
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28340413/design-synthesis-and-biological-evaluation-of-novel-coumarin-based-benzamides-as-potent-histone-deacetylase-inhibitors-and-anticancer-agents
#17
Tooba Abdizadeh, Mohammad Reza Kalani, Khalil Abnous, Zahra Tayarani-Najaran, Bibi Zahra Khashyarmanesh, Rahman Abdizadeh, Razieh Ghodsi, Farzin Hadizadeh
Histone deacetylases (HDACs) are attractive therapeutic targets for the treatment of cancer and other diseases. It has four classes (I-IV), among them especially class I isozyme are involved in promoting tumor cells proliferation, angiogenesis, differentiation, invasion and metastasis and also viable targets for cancer therapeutics. A novel series of coumarin-based benzamides was designed and synthesized as HDAC inhibitors. The cytotoxic activity of the synthesized compounds (8a-u) was evaluated against six human cancer cell lines including HCT116, A2780, MCF7, PC3, HL60 and A549 and a single normal cell line (Huvec)...
March 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28340357/ruthenium-complexes-with-phenylterpyridine-derivatives-target-cell-membrane-and-trigger-death-receptors-mediated-apoptosis-in-cancer-cells
#18
Zhiqin Deng, Pan Gao, Lianling Yu, Bin Ma, Yuanyuan You, Leung Chan, Chaoming Mei, Tianfeng Chen
Elucidation of the communication between metal complexes and cell membrane may provide useful information for rational design of metal-based anticancer drugs. Herein we synthesized a novel class of ruthenium (Ru) complexes containing phtpy derivatives (phtpy = phenylterpyridine), analyzed their structure-activity relationship and revealed their action mechanisms. The result showed that, the increase in the planarity of hydrophobic Ru complexes significantly enhanced their lipophilicity and cellular uptake...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28340300/synthesis-of-3-o-sulfated-oligosaccharides-to-understand-the-relationship-between-structures-and-functions-of-heparan-sulfate
#19
Zhangjie Wang, Po-Hung Hsieh, Yongmei Xu, David Thieker, Evangeline Juan En Chai, Shaoshuai Xie, Brian Cooley, Robert Woods, Lianli Chi, Jian Liu
The sulfation at the 3-OH position of glucosamine is an important modification in forming structural domains for heparan sulfate to enable its biological functions. Seven 3-O-sulfotransferase isoforms in the human genome are involved in the biosynthesis of 3-O-sulfated heparan sulfate. As a rare modification present in heparan sulfate, the availability of 3-O-sulfated oligosaccharides is very limited. Here, we report the use of a chemoenzymatic synthetic approach to synthesize six 3-O-sulfated oligosaccharides, including three hexasaccharides and three octasaccharides...
March 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28340138/a-life-without-worms
#20
Richard E Sanya, Gyaviira Nkurunungi, Irene Andia Biraro, Harriet Mpairwe, Alison M Elliott
Worms have co-evolved with humans over millions of years. To survive, they manipulate host systems by modulating immune responses so that they cause (in the majority of hosts) relatively subtle harm. Anthelminthic treatment has been promoted as a measure for averting worm specific pathology and to mitigate subtle morbidities which may include effects on anaemia, growth, cognitive function and economic activity. With our changing environment marked by rapid population growth, urbanisation, better hygiene practices and anthelminthic treatment, there has been a decline in worm infections and other infectious diseases and a rise in non-communicable diseases such as allergy, diabetes and cardiovascular disease...
March 18, 2017: Transactions of the Royal Society of Tropical Medicine and Hygiene
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