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https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#1
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28734595/arrhythmias-after-left-ventricular-assist-device-implantation-incidence-and-management
#2
REVIEW
Anis J Kadado, Joseph G Akar, James P Hummel
The use of mechanical circulatory support has become an increasingly common practice in patients with heart failure, whether used as bridge to transplantation or as destination therapy. The last couple of decades has seen a drastic change in the functioning of the left ventricular assist devices (LVAD), changing from the first generation devices running on pulsatile flow to the current continuous flow devices. Atrial and ventricular arrhythmias are common among heart failure patients, and though the systematic circulation is well supported in patients on mechanical circulatory support, these arrhythmias can still be the cause of detrimental symptoms and lead to potentially fatal outcomes...
July 10, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28733937/sequential-extraction-as-novel-approach-to-compare-12-medicinal-plants-from-kenya-regarding-their-potential-to-release-chromium-manganese-copper-and-zinc
#3
R Mogwasi, S Zor, D K Kariuki, M Z Getenga, V Nischwitz
This study is focusing on a novel approach to screen a large number of medicinal plants from Kenya regarding their contents and availability of selected metals potentially relevant for treatment of diabetes patients. For this purpose, total levels of zinc, chromium, manganese, and copper were determined by flame atomic absorption spectrometry and inductively coupled plasma mass spectrometry as well as BCR sequential extraction to fractionate the elemental species in anti-diabetic medicinal plants collected from five natural locations in two sub counties in Nyamira County, Kenya...
July 21, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28733200/hypothermic-cooling-measured-by-thermal-mri-imaging-feasibility-and-implications-for-virtual-imaging-in-the-urogenital-pelvis
#4
Douglas Skarecky, Hon Yu, Jennifer Linehan, Blanca Morales, Min-Ying Su, Peter Fwu, Thomas Ahlering
OBJECTIVE: To study the combination of thermal MRI imaging and novel hypothermic cooling, via an Endorectal Cooling Balloon (ECB) to assess the effective dispersion and temperature drop in pelvic tissue to potentially reduce inflammatory cascade in surgical applications. METHODS: Three male subjects, prior to undergoing robot-assisted radical prostatectomy (RARP), were cooled via an ECB, rendered MRI compatible by for patient safety Prior to ECB hypothermia. MRI studies were performed using a 3T scanner and included T2w anatomical scan for the pelvic structures, followed by a temperature mapping scan...
July 18, 2017: Urology
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#5
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28728565/identification-of-differential-co-expressed-gene-networks-in-early-rheumatoid-arthritis-achieving-sustained-drug-free-remission-after-treatment-with-a-tocilizumab-based-or-methotrexate-based-strategy
#6
Xavier M Teitsma, Johannes W G Jacobs, Michal Mokry, Michelle E A Borm, Attila Pethö-Schramm, Jacob M van Laar, Johannes W J Bijlsma, Floris P J Lafeber
BACKGROUND: Methotrexate is endorsed to be used as first-line treatment in rheumatoid arthritis (RA). However, a large proportion of patients need additional treatment with a biological disease-modifying anti-rheumatic drug (DMARD) to adequately suppress their disease activity. A better understanding of genotypes could help to distinguish between patients with different pathogenic mechanisms. The aim of this study was therefore to identify networks of genes within DMARD-naive early RA patients associated with achieving sustained drug-free remission (sDFR) after initiating tocilizumab plus methotrexate, tocilizumab, or methotrexate therapy...
July 20, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28727818/prep-in-italy-the-time-may-be-ripe-but-who-s-paying-the-bill-a-nationwide-survey-on-physicians-attitudes-towards-using-antiretrovirals-to-prevent-hiv-infection
#7
Antonio Di Biagio, Niccolò Riccardi, Alessio Signori, Renato Maserati, Silvia Nozza, Andrea Gori, Stefano Bonora, Marco Borderi, Diego Ripamonti, Maria Cristina Rossi, Giancarlo Orofino, Tiziana Quirino, Giuseppe Nunnari, Benedetto Maurizio Celesia, Salvatore Martini, Caterina Sagnelli, Giovanni Mazzola, Pietro Colletti, Dario Bartolozzi, Teresa Bini, Nicoletta Ladisa, Filippo Castelnuovo, Annalisa Saracino, Sergio Lo Caputo
Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28726521/polymer-donors-of-nitric-oxide-improve-the-treatment-of-experimental-solid-tumours-with-nanosized-polymer-therapeutics
#8
Milada Šírová, Veronika Horková, Tomáš Etrych, Petr Chytil, Blanka Říhová, Martin Studenovský
Polymer carriers based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with incorporated organic nitrates as nitric oxide (NO) donors were designed with the aim to localize NO generation in solid tumours, thus highly increasing the enhanced permeability and retention (EPR) effect. The NO donors were coupled to the polymer carrier either through a stable bond or through a hydrolytically degradable, pH sensitive, bond. In vivo, the co-administration of the polymer NO donor and HPMA copolymer-bound cytotoxic drug (doxorubicin; Dox) resulted in an improvement in the treatment of murine EL4 T-cell lymphoma...
July 20, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#9
Angelical S Martin, Dennis M Abraham, Kathleen A Hershberger, Dhaval P Bhatt, Lan Mao, Huaxia Cui, Juan Liu, Xiaojing Liu, Michael J Muehlbauer, Paul A Grimsrud, Jason W Locasale, R Mark Payne, Matthew D Hirschey
Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action exists via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich's ataxia cardiomyopathy mouse model (FXN-KO)...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28724547/long-term-effects-of-a-renin-inhibitor-versus-a-thiazide-diuretic-on-arterial-stiffness-and-left-ventricular-diastolic-function-in-elderly-hypertensive-patients
#10
Yoshiyuki Okada, Shigeki Shibata, Naoki Fujimoto, Stuart Alexander Best, Benjamin D Levine, Qi Fu
Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensives. Twenty one hypertensives [67±14 (SD) yrs] were randomly assigned to receive 6-month aliskiren (n=11) or hydrochlorothiazide (n=10) based therapy...
July 19, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28722668/coupling-to-a-cancer-selective-heparan-sulfate-targeted-branched-peptide-can-by-pass-breast-cancer-cell-resistance-to-methotrexate
#11
Lorenzo Depau, Jlenia Brunetti, Chiara Falciani, Silvia Scali, Giulia Riolo, Elisabetta Mandarini, Alessandro Pini, Luisa Bracci
Cancer-selective tetra-branched peptides, named NT4, can be coupled to different functional units for cancer cell imaging or therapy. NT4 peptides specifically bind to lipoprotein receptor-related proteins (LRP) receptors and to heparan sulfate chains on membrane proteoglycans and can be efficiently internalized by cancer cells expressing these membrane targets. Since binding and internalization of NT4 peptides is mediated by specific NT4 receptors on cancer cell membranes and this may allow drug resistance produced by drug membrane transporters to be by-passed, we tested the ability of drug-armed NT4 to by-pass drug resistance in cancer cell lines...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28721731/self-assembled-injectable-peptide-hydrogels-capable-of-triggering-antitumor-immune-response
#12
Ruirui Xing, Shukun Li, Ning Zhang, Guizhi Shen, Helmuth Möhwald, Xuehai Yan
Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and anti-tumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly-peptide (poly-L-lysine, PLL)...
July 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28721216/switch-to-restoration-therapy-in-a-testosterone-treated-central-hypogonadism-with-erythrocytosis
#13
B Cangiano, C Cacciatore, L Persani, M Bonomi
We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28720897/a-predictive-mathematical-modeling-approach-for-the-study-of-doxorubicin-treatment-in-triple-negative-breast-cancer
#14
Matthew T McKenna, Jared A Weis, Stephanie L Barnes, Darren R Tyson, Michael I Miga, Vito Quaranta, Thomas E Yankeelov
Doxorubicin forms the basis of chemotherapy regimens for several malignancies, including triple negative breast cancer (TNBC). Here, we present a coupled experimental/modeling approach to establish an in vitro pharmacokinetic/pharmacodynamic model to describe how the concentration and duration of doxorubicin therapy shape subsequent cell population dynamics. This work features a series of longitudinal fluorescence microscopy experiments that characterize (1) doxorubicin uptake dynamics in a panel of TNBC cell lines, and (2) cell population response to doxorubicin over 30 days...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720875/ruthenium-conjugated-chrysin-analogues-modulate-platelet-activity-thrombus-formation-and-haemostasis-with-enhanced-efficacy
#15
Divyashree Ravishankar, Maryam Salamah, Alda Attina, Radhika Pothi, Thomas M Vallance, Muhammad Javed, Harry F Williams, Eman M S Alzahrani, Elena Kabova, Rajendran Vaiyapuri, Kenneth Shankland, Jonathan Gibbins, Katja Strohfeldt, Francesca Greco, Helen M I Osborn, Sakthivel Vaiyapuri
The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720045/neonatal-acute-paronychia
#16
Luke Grome, Gregory Borah
BACKGROUND: Paronychia is defined as infection afflicting the eponychial nail folds of the hand or foot. Such infections are rarely reported in the perinatal age group, and not previously described in a neonate younger than 2 weeks. Trauma resulting in inoculation of the nail fold is the most common predisposing factor to paronychia. Oral trauma in the pediatric population from finger sucking predisposes this population to a different set of bacterial pathogens than adults. Contamination can progress to infection and abscess formation within the nail fold with the most prevalent vector in adult infections being Staphylococcus aureus...
February 1, 2017: Hand: Official Journal of the American Association for Hand Surgery
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#17
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28718772/performance-evaluation-of-macaco-a-multilayer-compton-camera
#18
Enrique Muñoz, John Barrio, Ane Etxebeste, Pablo Garcia Ortega, Carlos Lacasta, Josep Francisco Oliver, Carles Solaz, Gabriela Llosa
Compton imaging devices have been proposed and studied for a wide range of applications. We have developed a Compton camera prototype which can be operated with two or three detector layers based on monolithic lanthanum bromide (LaBr3) crystals coupled to silicon photomultipliers (SiPMs), to be used for proton range verification in hadron therapy. In this work, we present the results obtained with our prototype in laboratory tests with radioactive sources and in simulation studies...
July 18, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#19
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single-nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. While primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and solute carrier organic (SLCO) anion transporter, respectively OBJECTIVE: To investigate the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV) METHODS: Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients with an age range from 4...
July 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28717850/physio-biochemical-parameters-a-potential-tool-for-target-selective-treatment-of-haemonchosis-in-the-small-ruminants
#20
Bhupamani Das, Niranjan Kumar, Mehul M Jadav, Jayesh B Solanki, T K S Rao
This study aims to evaluate the conjunctiva colour-based FAMACHA score (FS) coupled with a body condition score (BCS), haemogram and stressor hormone level estimation, in identifying post-mortem (PM)/coproscopically proven individuals wanting therapy for economically important gastrointestinal (GI) helminths, Haemonchus contortus, in the small ruminants. The incidence of haemonchosis was significantly (p < 0.05) higher (60.81%) in the ruminants with FS = 3. The H. contortus count in the animals with FS 2, 3 and 4 was 23...
July 17, 2017: Tropical Animal Health and Production
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