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https://www.readbyqxmd.com/read/28346238/management-of-hypertension-in-2017-targets-and-therapies
#1
Monica Ahluwalia, Sripal Bangalore
PURPOSE OF REVIEW: Approximately one-fourth of the adult population is diagnosed with hypertension, which has been associated with increased cardiovascular morbidity and mortality including cardiovascular death, myocardial infarction, heart failure and stroke. Early detection and treatment is a key and can lead to a significant reduction in cardiovascular morbidity and mortality. RECENT FINDINGS: In this review, we discuss the management and treatment strategies in patients with hypertension in the current era...
March 24, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28346107/a-high-throughput-method-for-measuring-drug-residence-time-using-the-transcreener-adp-assay
#2
Meera Kumar, Robert G Lowery
Analysis of drug-target residence times during drug development can result in improved efficacy, increased therapeutic window, and reduced side effects. Residence time can be estimated as the reciprocal of the dissociation rate ( koff) of an inhibitor from its target. The traditional methods for measuring koff require synthesis of labeled ligands or low-throughput label-free methods. To provide an alternative that is better suited to an automated high-throughput screening (HTS) environment, we adapted a classic "jump dilution" catalytic assay method for determination of koff values for kinase inhibitor drugs...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346074/germline-genetic-predictors-of-aromatase-inhibitor-concentrations-estrogen-suppression-and-drug-efficacy-and-toxicity-in-breast-cancer-patients
#3
Daniel L Hertz, N Lynn Henry, James M Rae
The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28345874/delivery-of-pesticides-to-plant-parasitic-nematodes-using-tobacco-mild-green-mosaic-virus-as-a-nanocarrier
#4
Paul L Chariou, Nicole F Steinmetz
Plant parasitic nematodes are a major burden to the global agricultural industry, causing a $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides to be applied, putting the environment and human health at risk. Challenges are to treat nematodes that are located deep within the soil, feeding on the roots of plants. To attack the problem at its roots, we propose the use of tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as a carrier to deliver nematicides...
March 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28345753/outcomes-of-women-diagnosed-and-treated-for-low-risk-gestational-trophoblastic-neoplasia-at-the-queensland-trophoblast-centre-qtc
#5
Lisanne Verhoef, David Baartz, Shona Morrison, Karen Sanday, Andrea Janet Garrett
BACKGROUND: Gestational trophoblastic neoplasia (GTN) is classified as a highly curable group of pregnancy-related malignancies; however, approximately 15% will be persistent and require chemotherapy. Up to 25% of these women will develop resistance and 2% will develop disease relapse after initial chemotherapy. Despite the need for further chemotherapy in these women, cure rates are high. OBJECTIVE: To evaluate the outcomes of women diagnosed with low-risk GTN, assessing the type of treatment, the number of chemotherapy cycles received, development of resistance or disease relapse, survival, and to assess the feasibility of changing to a new drug regimen...
March 27, 2017: Australian & New Zealand Journal of Obstetrics & Gynaecology
https://www.readbyqxmd.com/read/28345463/computational-and-mechanistic-studies-on-the-effect-of-galactoxyloglucan-imatinib-nanoconjugate-in-imatinib-resistant-k562-cells
#6
Alphy Rose James, B S Unnikrishnan, R Priya, Manu M Joseph, T K Manojkumar, K Raveendran Pillai, R Shiji, G U Preethi, P Kusumakumary, T T Sreelekha
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345365/atrioventricular-nodal-ablation-in-patients-with-resynchronization-therapy-and-atrial-fibrillation-long-term-results
#7
Arleen Aune, Svein Færestrand, Per Ivar Hoff, Peter Schuster
OBJECTIVES: Atrioventricular nodal ablation (AVNA) is recommended for patients (pts) with cardiac resynchronization therapy (CRT) having atrial fibrillation (AF) and incomplete ventricular capture (Class IIa, level B). AVNA reduces mortality and improves the New York Heart Association (NYHA) functional class during intermediate term follow-up. The objectives were to study the long-term outcome regarding quality of life (QoL) and survival of our CRT pts after AVNA. DESIGN: 37 CRT-pts undergoing AVNA due to inadequate biventricular pacing were included in the study...
March 27, 2017: Scandinavian Cardiovascular Journal: SCJ
https://www.readbyqxmd.com/read/28344991/antibody-directed-glucocorticoid-targeting-to-cd163-in-m2-type-macrophages-attenuates-fructose-induced-liver-inflammatory-changes
#8
Pia Svendsen, Jonas H Graversen, Anders Etzerodt, Henrik Hager, Rasmus Røge, Henning Grønbæk, Erik I Christensen, Holger J Møller, Hendrik Vilstrup, Søren K Moestrup
Increased consumption of high-caloric carbohydrates contributes substantially to endemic non-alcoholic fatty liver disease in humans, covering a histological spectrum from fatty liver to steatohepatitis. Hypercaloric intake and lipogenetic effects of fructose and endotoxin-driven activation of liver macrophages are suggested to be essential to disease progression. In the present study, we show that a low dose of an anti-CD163-IgG-dexamethasone conjugate targeting the hemoglobin scavenger receptor CD163 in Kupffer cells and other M2-type macrophages has a profound effect on liver inflammatory changes in rats on a high-fructose diet...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#9
Jeanelle King, Javier de la Cruz, Jose Lutzky
BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28344477/development-and-characterization-of-methoxy-poly-ethylene-oxide-block-poly-%C3%AE%C2%B5-caprolactone-peo-b-pcl-micelles-as-vehicles-for-the-solubilization-and-delivery-of-tacrolimus
#10
Raisuddin Ali, Abubakar Farah, Ziyad Binkhathlan
Tacrolimus is a potent immunosuppressant; however, it suffers from several problems such as poor water solubility (4-12 μg/mL), low and variable oral bioavailability in patients, and narrow therapeutic window that could not be solved by the currently available i.v. formulation (Prograf®). Moreover, Prograf® contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions. Therefore, the aim of the present study was to investigate the potential of PEO-b-PCL polymeric micelles as alternative vehicles for the solubilization and delivery of tacrolimus...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344474/biologically-guided-isolation-of-leishmanicidal-secondary-metabolites-from-euphorbia-peplus-l
#11
Elham Amin, Abeer Moawad, Hossam Hassan
Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Moreover, the severe side effects and the reported drug resistance make it an urgent need to search for effective drugs that can replace or supplement those currently used. In a research program designed to investigate the antileishmanial activity of plants collected from the Egyptian flora, twenty extracts from fifteen plants growing in Egypt have been investigated for in vitro leishmanicidal activity against Leishmania donovani promastigotes...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344324/diallyl-trisulfide-suppresses-tumor-growth-through-the-attenuation-of-nrf2-akt-and-activation-of-p38-jnk-and-potentiates-cisplatin-efficacy-in-gastric-cancer-treatment
#12
Xiao-Yan Jiang, Xiao-Song Zhu, Hong-Ya Xu, Zhong-Xi Zhao, Si-Ying Li, Shan-Zhong Li, Jian-Hua Cai, Ji-Min Cao
Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 μmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115...
March 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28344323/new-knowledge-of-the-mechanisms-of-sorafenib-resistance-in-liver-cancer
#13
REVIEW
Yan-Jing Zhu, Bo Zheng, Hong-Yang Wang, Lei Chen
Sorafenib is an oral multikinase inhibitor that suppresses tumor cell proliferation and angiogenesis and promotes tumor cell apoptosis. It was approved by the FDA for the treatment of advanced renal cell carcinoma in 2006, and as a unique target drug for advanced hepatocellular carcinoma (HCC) in 2007. Sorafenib can significantly extend the median survival time of patients but only by 3-5 months. Moreover, it is associated with serious adverse side effects, and drug resistance often develops. Therefore, it is of great importance to explore the mechanisms underlying sorafenib resistance and to develop individualized therapeutic strategies for coping with these problems...
March 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28344147/evaluation-of-deprescribing-amiodarone-after-new-onset-atrial-fibrillation-in-critical-illness
#14
Areerut Leelathanalerk, Wannisa Dongtai, Yvonne Huckleberry, Brian Kopp, John Bloom, Joseph Alpert
BACKGROUND: Recent studies have shed light on the continued prescription of inpatient medications upon hospital discharge despite the original intent of short-term inpatient therapy. Amiodarone, an antiarrhythmic associated with significant adverse effects with long-term use, is commonly used for new-onset atrial fibrillation in critical illness (NAFCI). While it is often preferred in this setting of hemodynamic instability, a prescription for long-term use should be carefully considered, preferably by a cardiologist...
March 23, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28343935/blood-derived-products-in-pediatrics-new-laboratory-tools-for-optimizing-potency-assignment-and-reducing-side-effects
#15
REVIEW
Jean Amiral, Jerard Seghatchian
Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks...
March 15, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28343282/effective-chemotherapy-of-heterogeneous-and-drug-resistant-early-colon-cancers-by-intermittent-dose-schedules-a-computer-simulation-study
#16
David E Axelrod, Sudeepti Vedula, James Obaniyi
PURPOSE: The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function...
March 25, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28343197/-skin-cancers-in-kidney-transplant-recipients
#17
Anna Bieryło, Szymon Brzósko, Elżbieta Laudańska, Beata Naumnik
Kidney transplantation is the best treatment for end-stage renal failure. It prolongs the patient's life, improves quality of life and reduces costs associated with renal replacement therapy. Increasingly, newer immunosuppressive regimens allow for the proper functioning of the transplanted organ for many years. The progress in transplantation, qualification patients in older age for the procedure and longer survival of kidney graft lead to an increase in the number of patients receiving immunosuppressive drugs...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28342907/active-placebo-control-groups-of-pharmacological-interventions-were-rarely-used-but-merited-serious-consideration-a-methodological-overview
#18
Jakob Solgaard Jensen, Andreas Ørsted Bielefeldt, Asbjørn Hróbjartsson
OBJECTIVES: Active placebos are control interventions that mimic the side-effects of the experimental interventions in randomised trials and are sometimes used to reduce the risk of unblinding. We wanted to assess how often randomised clinical drug trials implement active placebo control groups; to provide a catalogue, and a characterisation, of such trials; and to analyse methodological arguments for and against use of active placebo. STUDY DESIGN: An overview consisting of three thematically linked sub-studies...
March 22, 2017: Journal of Clinical Epidemiology
https://www.readbyqxmd.com/read/28342779/suppression-of-calpain-expression-by-nsaids-is-associated-with-inhibition-of-cell-migration-in-rat-duodenum
#19
Kristopher Silver, A Littlejohn, Laurel Thomas, Bhupinder Bawa, James D Lillich
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the alleviation of pain and inflammation, but these drugs are also associated with a suite of negative side effects. Gastrointestinal (GI) toxicity is particularly concerning since it affects an estimated 70% of individuals taking NSAIDs routinely, and evidence suggests the majority of toxicity is occurring in the small intestine. Traditionally, NSAID-induced GI toxicity has been associated with indiscriminate inhibition of cyclooxygenase isoforms, but other mechanisms, including inhibition of cell migration, intestinal restitution, and wound healing, are likely to contribute to toxicity...
March 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28342204/the-ep4-antagonist-l-161-982-induces-apoptosis-cell-cycle-arrest-and-inhibits-prostaglandin-e2-induced-proliferation-in-oral-squamous-carcinoma-tca8113-cells
#20
Xiaohui Li, Bo Yang, Guoxu Han, Weizhong Li
BACKGROUND: Recent studies suggest that cyclooxygenase 2 (COX-2) inhibitors may enhance the toxic effects of anticancer drugs on tumor cells, including oral squamous cell carcinoma(OSCC), but its long-term use can cause side effects such as stomach ulcers and myocardial infarction. Our aim was to investigate proliferative effects of a downstream product of COX-2, prostaglandin E2(PGE2), in human oral squamous carcinoma cell line Tca8113 and explore the effects of PGE2 receptors, especially EP4 receptor, on the growth of Tca8113 cells...
March 25, 2017: Journal of Oral Pathology & Medicine
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