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https://www.readbyqxmd.com/read/28655182/longitudinal-changes-in-mean-and-pulse-pressure-and-all-cause-mortality-data-from-71-629-untreated-normotensive-individuals
#1
Athanase D Protogerou, Charalambos Vlachopoulos, Frederique Thomas, Yi Zhang, Bruno Pannier, Jacques Blacher, Michel E Safar
BACKGROUND: Blood pressure (BP) includes a steady (mean arterial pressure, MAP) and a pulsatile component that independently predict mortality. The association between longitudinal changes in central (c) pulse pressure (PP), brachial (b) PP, MAP, and incident mortality has never been investigated in this context. METHODS: Brachial MAP and PP were measured at 2 routine checkups (1st visit 1992; mean interval, 5.8 ± 2.4 years) in 71,629 individuals, age 16-95 years, none on antihypertensive drugs...
June 26, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28654954/bioequivalence-between-generic-and-branded-lamotrigine-in-people-with-epilepsy-the-equigen-randomized-clinical-trial
#2
Michel Berg, Timothy E Welty, Barry E Gidal, Francisco J Diaz, Ron Krebill, Jerzy P Szaflarski, Barbara A Dworetzky, John R Pollard, Edmund J Elder, Wenlei Jiang, Xiaohui Jiang, Regina D Switzer, Michael D Privitera
Importance: Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs. Objective: To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. Design, Setting, and Participants: The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers...
June 26, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28654904/digoxin-induced-anemia-among-patients-with-atrial-fibrillation-and-heart-failure-clinical-data-analysis-and-drug-gene-interaction-network
#3
Yubi Lin, Siqi He, Ruiling Feng, Zhe Xu, Wanqun Chen, Zifeng Huang, Yang Liu, Qianhuan Zhang, Bin Zhang, Kejian Wang, Shulin Wu
Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients. Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28654574/capecitabine-and-celecoxib-as-a-promising-therapy-for-thymic-neoplasms
#4
Kevin Wood, Elizabeth Byron, Linda Janisch, Ravi Salgia, Manish R Sharma
OBJECTIVES: For patients with unresectable or metastatic thymic epithelial neoplasms, few therapy options are available and outcomes are poor. This case series demonstrates that the combination of capecitabine and celecoxib may be a promising therapeutic option for these patients. MATERIALS AND METHODS: The current report describes the outcomes of 5 patients with thymic neoplasms treated on a drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies (NCT01705106) conducted at the University of Chicago, plus a sixth patient treated with the same regimen outside of the protocol...
June 26, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28654243/mitochondria-targeted-triphenylphosphonium-based-compounds-syntheses-mechanisms-of-action-and-therapeutic-and-diagnostic-applications
#5
Jacek Zielonka, Joy Joseph, Adam Sikora, Micael Hardy, Olivier Ouari, Jeannette Vasquez-Vivar, Gang Cheng, Marcos Lopez, Balaraman Kalyanaraman
Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules...
June 27, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#6
Michael B Bottorff, David R Bright, David F Kisor
Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to utilize pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether or not pharmacogenomics is cost-effective...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28653980/ligand-shaping-in-induced-fit-docking-of-mray-inhibitors-polynomial-discriminant-and-laplacian-operator-as-biological-activity-descriptors
#7
Claudiu N Lungu, Mircea V Diudea, Mihai V Putz
Docking-i.e., interaction of a small molecule (ligand) with a proteic structure (receptor)-represents the ground of drug action mechanism of the vast majority of bioactive chemicals. Ligand and receptor accommodate their geometry and energy, within this interaction, in the benefit of receptor-ligand complex. In an induced fit docking, the structure of ligand is most susceptible to changes in topology and energy, comparative to the receptor. These changes can be described by manifold hypersurfaces, in terms of polynomial discriminant and Laplacian operator...
June 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28653847/glucuronides-as-potential-anionic-substrates-of-human-cytochrome-p450-2c8-cyp2c8
#8
Yong Ma, Yue Fu, S Cyrus Khojasteh, Deepak Dalvie, Donglu Zhang
Glucuronidation is in general considered as a terminal metabolic step that leads to direct elimination of drugs and generally abolishes their biological activity. However, there is growing evidence to suggest that glucuronides can be ligands of human CYP2C8, making CYP2C8 distinct from the other CYP isoforms. Several classes of glucuronide conjugates, which include acyl glucuronides, ether glucuronides, N-glucuronides, and carbamoyl glucuronides, have been shown to be substrates or time-dependent inhibitors of CYP2C8...
June 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28653752/the-potential-of-epimedium-koreanum-nakai-for-herb-drug-interaction
#9
Qingxiang Zhong, Ziqi Shi, Li Zhang, Rongling Zhong, Zhi Xia, Jing Wang, Hao Wu, Yutong Jiang, E Sun, Yingjie Wei, Liang Feng, Zhenhai Zhang, Dan Liu, Jie Song, Xiaobin Jia
OBJECTIVES: This study aims to investigate potential herb-drug interactions (HDI) of Epimedium koreanum Nakai. METHODS: Human liver microsomes (HLMs) were used to determine the enzyme kinetics of the major human cytochrome P450s (CYPs). Inducible potential of E. koreanum on CYP1A2, 2B6, 2C19 and 3A4 activities of human primary hepatocytes was also examined. KEY FINDINGS: Ethanol extract of E. koreanum showed direct inhibitory potency for CYP1A2 (IC50  = 121...
June 27, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28653666/endocannabinoid-regulation-of-reward-and-reinforcement-through-interaction-with-dopamine-and-endogenous-opioid-signaling
#10
J M Wenzel, J F Cheer
The endocannabinoid system (eCB) is implicated in the mediation of both reward and reinforcement. This is evidenced by the ability of exogenous cannabinoid drugs to produce hedonia and maintain self-administration in both human and animal subjects. eCBs similarly facilitate behaviors motivated by reward through interaction with the mesolimbic dopamine (DA) and endogenous opioid systems. Indeed, eCB signaling in the ventral tegmental area (VTA) stimulates activation of midbrain DA cells and promotes DA release in terminal regions such as the nucleus accumbens (NAc)...
June 27, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28653073/electro-mechano-responsive-properties-of-gelatin-methacrylate-gelma-hydrogel-on-conducting-polymer-electrodes-quantified-using-atomic-force-microscopy
#11
Christina Puckert, Eva Tomaskovic-Crook, Sanjeev Gambhir, Gordon G Wallace, Jeremy M Crook, Michael J Higgins
Electrical stimulation of hydrogels has been performed to enable micro-actuation or controlled movement of ions and biomolecules such as in drug release applications. Hydrogels are also increasingly used as low modulus, biocompatible coatings on electrode devices and thus are exposed to the effects of electrical stimulation. As such, there is growing interest in the latter, especially on the dynamic and nanoscale physical properties of hydrogels. Here, we report on the electro-mechano properties of photocrosslinkable gelatin methacrylate (GelMA) hydrogel applied as coatings on conducting polymer polypyrrole-dodecylbenze sulfonate (PPy-DBSA) electrodes...
June 27, 2017: Soft Matter
https://www.readbyqxmd.com/read/28652917/photocrosslinkable-biodegradable-hydrogels-with-controlled-cell-adhesivity-for-prolonged-sirna-delivery-to-hmscs-to-enhance-their-osteogenic-differentiation
#12
Minh Khanh Nguyen, Alexandra McMillan, Cong Truc Huynh, Daniel S Schapira, Eben Alsberg
Photocrosslinked, biodegradable hydrogels have been extensively investigated for biomedical applications, including drug delivery and tissue engineering. Here, dextran (DEX) was chemically modified with mono(2-acryloyloxyethyl) succinate (MAES) via an esterification reaction, resulting in macromers that could be photocrosslinked to form hydrolytically degradable hydrogels. Hydrogel swelling ratio and degradation rate were controlled by varying the degree of MAES modification. Thiolated cell adhesion peptides (GRGDSPC) were conjugated to acrylated dextran via thiol-acrylate reaction to regulate the interactions of human mesenchymal stem cells (hMSCs) with the photocrosslinkable hydrogels...
January 21, 2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28652811/structure-based-virtual-screening-and-molecular-docking-for-the-identification-of-potential-multi-targeted-inhibitors-against-breast-cancer
#13
Zeeshan Yousuf, Kanzal Iman, Nauman Iftikhar, Muhammad Usman Mirza
Breast cancer is characterized by an uncontrolled growth of cells in breast tissue. Genes that foster cell growth in breast cells are overexpressed, giving rise to breast tumors. The identification of effective inhibitors represents a rational chemopreventive strategy. The current in silico study provides a pharmacoinformatic approach for the identification of active compounds against a co-chaperone HSP90 and the human epidermal growth factor receptors EGFR and HER2/neu receptor. The elevated levels of expression of these target proteins have been documented in breast cancer...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28652716/can-we-improve-pain-and-sleep-in-elderly-individuals-with-transcranial-direct-current-stimulation-results-from-a-randomized-controlled-pilot-study
#14
Marie-Philippe Harvey, Dominique Lorrain, Marylie Martel, Kayla Bergeron-Vezina, Francis Houde, Mario Séguin, Guillaume Léonard
BACKGROUND: The prevalence of chronic pain and sleep disturbances substantially increases with age. Pharmacotherapy remains the primary treatment option for these health issues. However, side effects and drug interactions are difficult to control in elderly individuals. AIMS: The objective of this study was to assess the feasibility of conducting a randomized sham-controlled trial and to collect preliminary data on the efficacy of transcranial direct current stimulation (tDCS) to reduce pain and improve sleep in older adults suffering from chronic pain...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28652338/optimal-multivalent-targeting-of-membranes-with-many-distinct-receptors
#15
Tine Curk, Jure Dobnikar, Daan Frenkel
Cells can often be recognized by the concentrations of receptors expressed on their surface. For better (targeted drug treatment) or worse (targeted infection by pathogens), it is clearly important to be able to target cells selectively. A good targeting strategy would result in strong binding to cells with the desired receptor profile and barely binding to other cells. Using a simple model, we formulate optimal design rules for multivalent particles that allow them to distinguish target cells based on their receptor profile...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28652330/exploiting-the-synthetic-lethality-between-terminal-respiratory-oxidases-to-kill-mycobacterium-tuberculosis-and-clear-host-infection
#16
Nitin P Kalia, Erik J Hasenoehrl, Nurlilah B Ab Rahman, Vanessa H Koh, Michelle L T Ang, Dannah R Sajorda, Kiel Hards, Gerhard Grüber, Sylvie Alonso, Gregory M Cook, Michael Berney, Kevin Pethe
The recent discovery of small molecules targeting the cytochrome bc1 :aa3 in Mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. The mycobacterial cytochrome bc1 :aa3 consists of a menaquinone:cytochrome c reductase (bc1 ) and a cytochrome aa3 -type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. Despite the affinity of Q203 for the bc1 :aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters...
June 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28652278/palbociclib-combined-with-fulvestrant-in-premenopausal-women-with-advanced-breast-cancer-and-prior-progression-on-endocrine-therapy-paloma-3-results
#17
Sibylle Loibl, Nicholas C Turner, Jungsil Ro, Massimo Cristofanilli, Hiroji Iwata, Seock-Ah Im, Norikazu Masuda, Sherene Loi, Fabrice André, Nadia Harbeck, Sunil Verma, Elizabeth Folkerd, Kathy Puyana Theall, Justin Hoffman, Ke Zhang, Cynthia Huang Bartlett, Mitchell Dowsett
BACKGROUND: The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). PATIENTS AND METHODS: One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo...
June 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28652220/inhibition-of-alzheimer-s-amyloid-beta-aggregation-in-vitro-by-carbenoxolone-insight-into-mechanism-of-action
#18
Sheetal Sharma, Bimla Nehru, Avneet Saini
BACKGROUND: The major hallmark of Alzheimer's disease (AD) is the formation of amyloid aggregates, which are formed due to improper folding of proteins leading to the aggregation of amyloid beta (Aβ) 42 peptide. Inhibition of Aβ 42 aggregation using a drug such as carbenoxolone (Cbx), which has already been stated as neuroprotective, appears to be an effective approach against AD. OBJECTIVE: The present study was designed to investigate the anti-fibrillation activity of Cbx against the Aβ 42 aggregation...
June 23, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28652206/membrane-solid-state-nmr-in-canada-a-historical-perspective
#19
REVIEW
Michèle Auger
This manuscript presents an overview of more than 40years of membrane solid-state nuclear magnetic resonance (NMR) research in Canada. This technique is a method of choice for the study of the structure and dynamics of lipid bilayers; bilayer interactions with a variety of molecules such as membrane peptides, membrane proteins and drugs; and to investigate membrane peptide and protein structure, dynamics, and topology. Canada has a long tradition in this field of research, starting with pioneering work on natural and model membranes in the 1970s in a context of emergence of biophysics in the country...
June 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28652172/enhancement-and-inhibition-effects-on-the-corneal-permeability-of-timolol-maleate-polymers-cyclodextrins-and-chelating-agents
#20
Isabel Rodriguez, José Antonio Vázquez, Lorenzo Pastrana, Vitaliy V Khutoryanskiy
This study investigates how both bioadhesive polymers (chitosan, hyaluronic acid and alginate) and permeability enhancers (ethylene glycol- bis(2-aminoethylether)- N, N, N', N'- tetraacetic acid (EGTA) and hydroxypropyl-ß-cyclodextrin) influence the permeability of the anti-glaucoma drug timolol maleate through ex vivo bovine corneas. Our results showed that only the permeability enhancers alone were able to increase drug permeability, whereas the polymers significantly reduced drug permeation, and however, they increased the pre-corneal residence of timolol...
June 23, 2017: International Journal of Pharmaceutics
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