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https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#1
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28636192/intestinal-barrier-integrity-and-inflammatory-bowel-disease-stem-cell-based-approaches-to-regenerate-the-barrier
#2
REVIEW
Fredrik E O Holmberg, Jannie Pedersen, Peter Jørgensen, Christoffer Soendergaard, Kim B Jensen, Ole H Nielsen
Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, which includes increased epithelial cell death, modified mucus configuration, altered expression and distribution of tight junction-proteins, along with a decreased expression of antimicrobial peptides. Inflammatory bowel disease is associated with life-long morbidity for affected patients, and both the incidence and prevalence is increasing globally, resulting in substantial economic strain for society...
June 21, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28636155/the-use-of-transnasal-humidified-rapid-insufflation-ventilatory-exchange-thrive-in-17-cases-of-subglottic-stenosis
#3
Kim To, Fleur Harding, McNeill Scott, Pamela Milligan, Iain J Nixon, Richard Adamson, Alistair F McNarry
Shared airway management in patients with subglottic stenosis (SGS) is challenging for both the anaesthetist and surgeon. Various methods of airway management have been described but currently no gold standard exists. Jet ventilation has been described as the preferred technique despite a UK National Survey highlighting potential complications including pneumothorax, pneumomediastinum, surgical emphysema, hypoxia and death. This article is protected by copyright. All rights reserved.
June 21, 2017: Clinical Otolaryngology
https://www.readbyqxmd.com/read/28636149/photocatalytic-interaction-of-aminophylline-riboflavin-leads-to-ros-mediated-dna-damage-and-cell-death-a-novel-phototherapeutic-mechanism-for-cancer
#4
Saniyya Khan, Imrana Naseem
The accompanied tissue devastation and systemic toxicity of chemotherapy has shifted the quest for having an effective and palliative cancer therapy towards photodynamic therapy (PDT). Riboflavin (Rf), an essential micronutrient is emerging as a potent tool of PDT, due to its excellent photosensitizing properties. It can be used as an efficient adjuvant for various anticancer drugs. The hemolytic and proteolytic effect of photoilluminated aminophylline (Am), a xanthine derivative, and Rf is well documented in literature...
June 21, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#5
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636139/review-of-hplc-and-lc-ms-ms-assays-for-the-determination-of-various-non-steroidal-anti-androgens-nsaa-used-in-the-treatment-of-prostate-cancer
#6
REVIEW
P S Suresh, Nuggehally R Srinivas, Ramesh Mullangi
Prostate cancer is the most common cancer and one of the leading causes for cancer deaths in men. One of the commonly used approaches to treat metastatic prostate cancer was via first generation non-steroidal anti-androgens (NSAA) namely flutamide, nilutamide, bicalutamide and topilutamide. Most of the prostate cancer patients who are initially responsive develop a most aggressive form of disease called castration-resistant prostate cancer (CRPC). Second generation NSAA receptor antagonists (enzalutamide, apalutamide and darolutamide) are emerging as additional new options to treat CRPC...
June 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28635954/phenotypic-extremes-of-bicd2-opathies-from-lethal-congenital-muscular-atrophy-with-arthrogryposis-to-asymptomatic-with-subclinical-features
#7
Markus Storbeck, Beate Horsberg Eriksen, Andreas Unger, Irmgard Hölker, Ingvild Aukrust, Lilian A Martínez-Carrera, Wolfgang A Linke, Andreas Ferbert, Raoul Heller, Matthias Vorgerd, Gunnar Houge, Brunhilde Wirth
Heterozygous variants in BICD cargo adapter 2 (BICD2) cause autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 (SMALED2). The disease is usually characterized by a benign or slowly progressive, congenital or early onset muscle weakness and atrophy that mainly affects the lower extremities, although some affected individuals show involvement of the arms and the shoulder girdle. Here we report unusual extremes of BICD2-related diseases: A severe form of congenital muscular atrophy with arthrogryposis multiplex, respiratory insufficiency and lethality within four months...
June 21, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28635909/-chronic-obstructive-pulmonary-disease-concurrent-with-metabolic-syndrome-pathophysiological-and-clinical-features
#8
A V Budnevsky, E S Ovsyannikov, N B Labzhania
Chronic obstructive pulmonary disease (COPD) still remains a serious public health problem, which is a common cause of disability and death in the able-bodied population. Furthermore, the number of patients with metabolic syndrome (MS) is steadily increasing worldwide. Recently, there is also an increase in the number of patients with COPD concurrent with MS, which is a mutually confounding risk factor for concomitant cardiovascular disease and adversely affects prognosis in these patients. Systemic subclinical inflammation is a common link between COPD and the components of MS...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28635905/-algorithm-for-the-management-of-patients-with-stable-coronary-artery-disease-and-high-grade-ventricular-arrhythmias
#9
Е А Ryngach, T V Treshkur, A A Tatarinova, E V Shlyakhto
The paper gives an original algorithm for the management of patients with stable coronary artery disease, preserved/moderately reduced left ventricular systolic function, and high-grade ventricular arrhythmias from the first registration of the latter to the choice of treatment policy. Great attention is paid to the assessment of a private clinical case, by determining the nature of arrhythmias, and to the involvement of autonomic regulation in the genesis of ventricular arrhythmias. The importance of topical diagnosis of ventricular arrhythmias and identification of psychological disorders is emphasized...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28635673/toxicity-of-naphthalene-and-benzene-on-tribollium-castaneum-herbst
#10
Nerlis Pajaro-Castro, Karina Caballero-Gallardo, Jesus Olivero-Verbel
Naphthalene and benzene are widely-used volatile organic compounds. The aim of this research was to examine the toxicological effects of naphthalene and benzene against Tribolium castaneum as an animal model. Adult insects were exposed to these aromatic compounds to assess mortality after 4-48 h of exposure. The lethal concentration 50 (LC50) for naphthalene, naphthalin, and benzene were 63.6 µL/L, 20.0 µL/L, and 115.9 µL/L in air, respectively. Real-time polymerase chain reaction (PCR) analysis revealed expression changes in genes related to oxidative stress and metabolism [Glutathione S-Transferase (Gst), and Cytochrome P450 6BQ8 (Cyp6bq8)]; reproduction and metamorphosis [Hormone receptor in 39-like protein (Hr39), Ecdysone receptor: (Ecr), and Chitin synthase 2 (Chs2)]; and neurotransmission [Histamine-gated chloride channel 2 (Hiscl2)] in insects exposed for 4 h to 70...
June 21, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28635661/hypoxic-preconditioning-promotes-the-bioactivities-of-mesenchymal-stem-cells-via-the-hif-1%C3%AE-grp78-akt-axis
#11
Jun Hee Lee, Yeo Min Yoon, Sang Hun Lee
Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#12
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635648/deoxyelephantopin-and-isodeoxyelephantopin-as-potential-anticancer-agents-with-effects-on-multiple-signaling-pathways
#13
REVIEW
Tahir Mehmood, Amara Maryam, Hamed A Ghramh, Muhammad Khan, Tonghui Ma
Cancer is the 2nd leading cause of death worldwide. The development of drugs to target only one specific signaling pathway has limited therapeutic success. Developing chemotherapeutics to target multiple signaling pathways has emerged as a new prototype for cancer treatment. Deoxyelephantopin (DET) and isodeoxyelephantopin (IDET) are sesquiterpene lactone components of "Elephantopus scaber and Elephantopus carolinianus", traditional Chinese medicinal herbs that have long been used as folk medicines to treat liver diseases, diabetes, diuresis, bronchitis, fever, diarrhea, dysentery, cancer, and inflammation...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#14
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#15
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635519/the-elicitor-protein-ases-induces-a-sar-response-accompanied-by-systemic-microbursts-and-micro-hrs-in-fragaria-ananassa
#16
Verónica Hael Conrad, Silvia Marisa Perato, Marta Elena Arias, Martín Gustavo Martínez Zamora, Pía de Los Ángeles Di Peto, Gustavo Gabriel Martos, Atilio Pedro Castagnaro, Juan Carlos Diaz-Ricci, Nadia Regina Chalfoun
The elicitor AsES (Acremonium strictum Elicitor Subtilisin) is a 34 KDa subtilisin-like protein secreted by the opportunistic fungus Acremonium strictum. AsES activates the innate immunity and confers resistance against anthracnose and grey mold diseases in strawberry plants (Fragaria x ananassa Duch.) and the last disease also in Arabidopsis. In the present work, we show that upon AsES recognition, a cascade of defense responses is activated, including: calcium influx, biphasic oxidative burst (O2(.-) and H2O2), HR response, accumulation of autofluorescent compounds, cell wall reinforcement with callose and lignin deposition, salicylic acid accumulation, and expression of defense-related genes such as FaPR1, FaPG1, FaMYB30, FaRBOH-D, FaRBOH-F, FaCHI23 and FaFLS...
June 21, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28635449/nursing-care-after-death-in-northern-ireland
#17
Lynne Pearce
Essential facts According to the Registrar General Annual Report, there were 15,548 deaths in Northern Ireland in 2015. Almost two thirds of these were of people aged 75 or over, and almost half occurred in NHS hospitals, with a further 20% in other hospitals or nursing homes. There are significant differences between what happens after death in Northern Ireland and in other UK countries. For example, in Northern Ireland it is common practice to hold a wake, where family and friends come together to view the deceased person in their home...
June 21, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28635446/child-deaths-from-diarrhoea-down-but-stay-highest-in-poorest-nations
#18
(no author information available yet)
The number of child deaths caused by diarrhoea globally has fallen by a third in ten years, research shows.
June 21, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28635435/gps-views-and-perspectives-on-patient-non-adherence-to-treatment-in-primary-care-prior-to-suicide
#19
Pooja Saini, Khatidja Chantler, Navneet Kapur
BACKGROUND: Individuals who do not adhere to their treatment regimens may be at greater risk of suicide but these issues are relatively unexplored in primary care services. AIM: To explore GPs' views and perspectives on the reasons why patients who were in contact with mental health services in the year prior to suicide was non-adherent to treatment prior to their death. METHOD: In total, 198 semi-structured face-to-face interviews with GPs of people who had died by suicide...
March 1, 2017: Journal of Mental Health
https://www.readbyqxmd.com/read/28635372/peptide-functionalized-nanoparticles-for-the-selective-induction-of-apoptosis-in-target-cells
#20
Nicole Remaliah S Sibuyi, Ntevheleni Thovhogi, Kwazikwakhe B Gabuza, Miche D Meyer, Mustafa Drah, Martin O Onani, Amanda Skepu, Abram M Madiehe, Mervin Meyer
AIM: The study developed a prohibitin (PHB) targeted nanotherapy for selective induction of apoptosis in target cells. METHODS: Gold nanoparticles (AuNPs) were bifunctionalized with adipose homing and proapoptotic peptides. The efficacy and mode of cell death induced by the AuNPs were investigated in vitro on three cancer cell lines. RESULTS: The antiproliferative activity of PHB-targeted bifunctionalized AuNPs was more pronounced on cells that express the PHB receptor, and demonstrated receptor-mediated targeting and selectivity...
June 21, 2017: Nanomedicine
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