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https://www.readbyqxmd.com/read/27915478/targeting-the-phosphatidylinositol-3-kinase-pathway-in-gastric-cancer-can-omics-improve-outcomes
#1
REVIEW
Phu Tran, Cham Nguyen, Samuel J Klempner
Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed...
November 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/27915325/possible-role-of-sildenafil-citrate-in-the-recurrence-of-neovascularization-in-laser-regressed-aggressive-posterior-rop
#2
Chaitra Jayadev, Phanibhushan Ramasastry, Alia Gul, Anand Vinekar
BACKGROUND: Systemic diseases and their treatment influence aggressive posterior retinopathy of prematurity. CASE CHARACTERISTICS: A premature infant with aggressive posterior retinopathy of prematurity underwent laser treatment with a favourable outcome. She was started on oral sidenafil citrate for pulmonary hypertension. Ten days later she developed neovascularization within the lasered retina. INTERVENTION/OUTCOME: Considering the possible role of sildenafil in this unusual development, the drug was withdrawn resulting in regression of the neovascularization...
November 7, 2016: Indian Pediatrics
https://www.readbyqxmd.com/read/27915304/invasive-aspergillosis-in-acute-myeloid-leukemia-are-we-making-progress-in-reducing-mortality
#3
Giulia Dragonetti, Marianna Criscuolo, Luana Fianchi, Livio Pagano
The incidence of invasive fungal disease (IFD) has varied during the last decades. However, over the years, we have observed a progressive reduction of mortality, mainly due to wider use of prophylactic antifungal therapy (i.e., new azoles, such as posaconazole), the development of new and more effective antifungal drugs (lipid compounds of amphotericin B, candins, and azoles of the previous generation) and improvement of diagnostic tools. Based on a number of international studies across three decades, the attributable mortality rate for IFD and invasive aspergillosis (IA) among patients with acute myeloid leukemia (AML) has progressively declined...
December 2, 2016: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/27915208/maximizing-the-impact-of-physiologically-based-oral-absorption-modeling-and-simulation
#4
John I Chung, Ron C Kelly, Jan Wahlstrom, Benjamin Wu, Tian Wu, Fernando Alvarez-Nunez
The challenge of bringing innovative medicines to patients in combination with intense competition within the pharmaceutical industry have induced companies to develop quality medicines more efficiently and cost-effectively. State-of-the art approaches to advance drug development have never been so urgent. One such approach that has been gaining traction within the industry is the application of modeling and simulation. In this commentary, the benefits of physiologically-based oral absorption (PBOA) modeling and simulation in drug development are highlighted and suggestions for maximizing its impact are provided...
November 30, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27915192/the-profiling-of-the-metabolites-of-hirsutine-in-rat-by-ultra-high-performance-liquid-chromatography-coupled-with-linear-ion-trap-orbitrap-mass-spectrometry-an-improved-strategy-for-the-systematic-screening-and-identification-of-metabolites-in-multi-samples
#5
Jianwei Wang, Peng Qi, Jinjun Hou, Yao Shen, Min Yang, Qirui Bi, Yanping Deng, Xiaojian Shi, Ruihong Feng, Zijin Feng, Wanying Wu, Dean Guo
Drug metabolites identification and construction of metabolic profile are meaningful work for the drug discovery and development. The great challenge during this process is the work of the structural clarification of possible metabolites in the complicated biological matrix, which often resulting in a huge amount data sets, especially in multi-samples in vivo. Analyzing these complex data manually is time-consuming and laborious. The object of this study was to develop a practical strategy for screening and identifying of metabolites from multiple biological samples efficiently...
November 21, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27915083/pharmacodynamic-and-cytogenetic-evaluation-in-cyp2c19-2-and-cyp2c19-3-allelomorphism-in-south-indian-population-with-clopidogrel-therapy
#6
Javeed Ahmad Tantray, K Pratap Reddy, Kaiser Jamil, Y Shiva Kumar
BACKGROUND: Genetic factors play a significant role in pathogenesis of most diseases of heart. The present study was undertaken to correlate coronary artery disease with demographical, biochemical alterations, SNPs, gene expression and chromosomal abnormalities and for further enlightening the investigation in this field. METHODS: 150 patients taking clopidogrel drug were selected and single nucleotide polymorphism was done by PCR-RFLP techniques. With the same patients cytogenetic analysis was carried out on leukocyte cultures by karyotyping...
November 11, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27915042/non-coding-rnas-and-berberine-a-new-mechanism-of-its-anti-diabetic-activities
#7
REVIEW
Wenguang Chang
Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27915009/exploring-gastrointestinal-variables-affecting-drug-and-formulation-behavior-methodologies-challenges-and-opportunities
#8
REVIEW
Bart Hens, Maura Corsetti, Robin Spiller, Luca Marciani, Tim Vanuytsel, Jan Tack, Arjang Talattof, Gordon L Amidon, Mirko Koziolek, Werner Weitschies, Clive G Wilson, Roelof J Bennink, Joachim Brouwers, Patrick Augustijns
Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologies (invasive versus non-invasive) to explore the impact of physiological variables on formulation behavior in the human GI tract are presented, revealing their strengths and limitations...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27914995/transdermal-skin-patch-based-on-reduced-graphene-oxide-a-new-approach-for-photothermal-triggered-permeation-of-ondansetron-across-porcine-skin
#9
Florina Teodorescu, Gurvan Quéniat, Catherine Foulon, Marie Lecoeur, Alexandre Barras, Samia Boulahneche, Mohmaed Salah Medjram, Thomas Hubert, Amar Abderrahmani, Rabah Boukherroub, Sabine Szunerits
The development of a skin-mounted patch capable of controlled transcutaneous delivery of therapeutics through thermal activation provides a unique solution for the controlled release of active principles over long-term periods. Here, we report on a flexible transdermal patch for photothermal triggered release of ondansetron (ODS), a commonly used drug for the treatment of chemotherapy-induced nausea and vomiting and used as model compound here. To achieve this, a dispersion of ODS-loaded reduced graphene oxide (rGO-ODS) nanosheets were deposited onto Kapton to produce a flexible polyimide-based patch...
November 30, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27914985/combination-therapy-with-doxorubicin-loaded-galactosylated-poly-ethyleneglycol-lithocholic-acid-to-suppress-the-tumor-growth-in-an-orthotopic-mouse-model-of-liver-cancer
#10
Bijay Singh, Yoonjeong Jang, Sushila Maharjan, Hyeon-Jeong Kim, Ah Young Lee, Sanghwa Kim, Nomundelger Gankhuyag, Myeon-Sik Yang, Yun-Jaie Choi, Myung-Haing Cho, Chong-Su Cho
Despite advances in technology, neither conventional anti-cancer drugs nor current nanoparticle (NP) drugs have gained substantial success in cancer treatment. While conventional chemotherapy drugs have several limitations such as low potency, poor in vivo stability and limited bioavailability, non-specific targeting of NP drugs diminishes their potency at actual target sites. In addition, the development of drug resistance to anti-cancer drugs is another challenging problem. To overcome these limitations, we aimed to develop a polymer-drug conjugate, which functions as an active NP drug and drug carrier both, to deliver a chemotherapeutic drug for combination therapy...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27914981/complement-a-primer-for-the-coming-therapeutic-revolution
#11
REVIEW
Scott R Barnum
The complement system is an important part of the innate and adaptive immune systems. Originally characterized as a single serum component contributing to the killing of bacteria, we now know that there are close to sixty complement proteins, multiple activation pathways and a wide range of effector functions mediated by complement. The system plays a critical role in host defense against bacteria, viruses, fungi and other pathogens. However, inappropriate complement activation contributes to the pathophysiology of autoimmune diseases and many inflammatory syndromes...
November 30, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27914949/anion-inhibition-profiles-of-the-%C3%AE-carbonic-anhydrase-from-the-pathogenic-bacterium-burkholderia-pseudomallei-responsible-of-melioidosis-and-highly-drug-resistant-to-common-antibiotics
#12
Sonia Del Prete, Daniela Vullo, Pietro Di Fonzo, Sameh M Osman, Zeid AlOthman, Claudiu T Supuran, Clemente Capasso
Burkholderia pseudomallei is a Gram-negative saprophytic bacterium responsible of melioidosis, an endemic disease of tropical and sub-tropical regions of the world. A recombinant γ-CA (BpsγCA) identified in the genome of this bacterium was cloned and purified. Its catalytic activity and anion inhibition profiles were investigated. The enzyme was an efficient catalyst for the CO2 hydration showing a kcat of 5.3×10(5)s(-1) and kcat/Km of 2.5×10(7)M(-1)×s(-1). The best BpsγCA inhibitors were sulfamide, sulfamic acid, phenylboronic acid and phenylarsonic acid, which showed KI in the range of 49-83μM (these inhibitors showed millimolar inhibition constant against hCA II), followed by diethyldithiocarbamate, selenate, tellurate, perrhenate, selenocyanate, trithiocarbonate, tetraborato, pyrophosphate, stannate, carbonate, bicarbonate, azide, cyanide, thiocyanate and cyanate with KIs in the range of 0...
November 14, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27914861/rapid-human-immunodeficiency-virus-testing-and-risk-prevention-in-residents-of-battered-women-s-shelters
#13
Dawn M Johnson, Nicole L Johnson, Curt G Beckwith, Patrick A Palmieri, Caron Zlotnick
BACKGROUND: Human immunodeficiency virus (HIV) infection and intimate partner violence (IPV) are interconnected public health problems. However, few HIV prevention interventions address the unique needs of IPV survivors in shelter and none of the Centers for Disease Control and Prevention's best-evidence risk reduction interventions adequately explore the complex relationship between IPV and HIV risk. Although battered women's shelters provide a safe and supportive environment for women in crisis, most do not offer HIV risk reduction services or sexual safety planning...
November 30, 2016: Women's Health Issues: Official Publication of the Jacobs Institute of Women's Health
https://www.readbyqxmd.com/read/27914853/monitoring-the-fitness-of-antiviral-resistant-influenza-strains-during-an-epidemic-a-mathematical-modelling-study
#14
Kathy Leung, Marc Lipsitch, Kwok Yung Yuen, Joseph T Wu
BACKGROUND: Antivirals (eg, oseltamivir) are important for mitigating influenza epidemics. In 2007, an oseltamivir-resistant influenza seasonal A H1N1 strain emerged and spread to global fixation within 1 year. This event showed that antiviral-resistant (AVR) strains can be intrinsically more transmissible than their contemporaneous antiviral-sensitive (AVS) counterpart. Surveillance of AVR fitness is therefore essential. Our objective was to develop a simple method for estimating AVR fitness from surveillance data...
November 30, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27914852/a-call-to-strengthen-the-global-strategy-against-schistosomiasis-and-soil-transmitted-helminthiasis-the-time-is-now
#15
REVIEW
Nathan C Lo, David G Addiss, Peter J Hotez, Charles H King, J Russell Stothard, Darin S Evans, Daniel G Colley, William Lin, Jean T Coulibaly, Amaya L Bustinduy, Giovanna Raso, Eran Bendavid, Isaac I Bogoch, Alan Fenwick, Lorenzo Savioli, David Molyneux, Jürg Utzinger, Jason R Andrews
In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy...
November 30, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27914799/computational-approach-for-the-assessment-of-inhibitory-potency-against-beta-amyloid-aggregation
#16
Marek Bajda, Sławomir Filipek
Beta-amyloid (Aβ) plaques are one of the hallmarks of Alzheimer's disease. Their presence in the brain leads to neurodegeneration and memory decline. Therefore, search for new drugs able to decrease formation of such deposits is of great interest. Our previously developed multifunctional compounds inhibited transformation of monomers into fibrils. Herein, we describe the computational approach for the assessment of inhibitory activity against Aβ aggregation. The influence of novel inhibitors on amyloid Aβ17-42 was studied by employing of molecular docking and all-atom molecular dynamics simulations...
November 24, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27914793/challenges-in-translational-development-of-pharmaceutical-cocrystals
#17
Dnyaneshwar P Kale, Sandeep S Zode, Arvind K Bansal
The last 2 decades have witnessed increased research in the area of cocrystals resulting in deeper scientific understanding, increase in intellectual property landscape, and evolution in the regulatory environment. Pharmaceutical cocrystals have received significant attention as a new solid form on account of their ability to modulate poor physicochemical properties of drug molecules. However, pharmaceutical development of cocrystals could be challenging, thus limiting their translation into viable drug products...
November 30, 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27914769/clinicopathological-and-molecular-characteristics-of-ku-70-80-expression-in-nigerian-breast-cancer-and-its-potential-therapeutic-implications
#18
Ayodeji O J Agboola, Henry O Ebili, Victoria O Iyawe, Adekunbiola A F Banjo, Babatunde A Salami, Emad A Rakha, Chrstopher C Nolan, Ian O Ellis, Andrew R Green
Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management...
October 25, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27914728/-nanotechnology-a-new-paradigm-in-atherosclerosis-treatment
#19
Virna M Martín Giménez, María Belén Ruiz-Roso, Alejandra Beatriz Camargo, Diego Kassuha, Walter Manucha
Atherosclerosis, a known and prevalent disease, causes progressive deterioration of affected vessels, inducing a blood flow reduction with different complications, and its symptoms usually manifest in advanced stages of the disease. Therefore, the classic therapeutic alternatives are insufficient because the damages are many times irreversible. For this reason, there is a need to implement intelligent forms of drug administration and develop new therapeutic targets that reduce the progression of atherosclerotic lesion...
November 30, 2016: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/27914632/the-us-food-and-drug-administration-s-risk-evaluation-and-mitigation-strategy-rems-program-current-status-and-future-direction
#20
Jasmanda Wu, Juhaeri Juhaeri
The US Food and Drug Administration (FDA) Amendments Act of 2007 granted the FDA new authorities to enhance drug safety by requiring application holders to submit a proposed Risk Evaluation and Mitigation Strategy (REMS). A REMS is a required risk management plan that uses tools beyond the package insert. REMS elements may include a medication guide and patient package insert for patients and a communication plan focused on health care professionals. Elements to assure safe use (ETASUs) are put in place to mitigate a specific known serious risk when other less restrictive elements of a REMS are not sufficient to mitigate such risk...
November 30, 2016: Clinical Therapeutics
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