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Drugs in emergency

Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Eric B Elbogen, H Ryan Wagner, Mira Brancu, Nathan A Kimbrel, Jennifer C Naylor, Cindy M Swinkels, John A Fairbank
Introduction: In response to a strong focus on suicide prevention for all veterans, the Department of Veterans Affairs (VA) recently revised policy to provide emergency mental healthcare for veterans who received Other Than Honorable (OTH) discharges from the military. This current study takes a preliminary step toward identifying demographic, historic, military, clinical, and social characteristics of veterans with OTH discharges. Materials and Methods: N = 1,172 Iraq/Afghanistan-era veterans were evaluated between 2005 and 2016 in the multi-site VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (MIRECC) Study of Post-Deployment Mental Health (PDMH Study)...
March 14, 2018: Military Medicine
Mousumi Pal, Utpal Nandi, Debaraj Mukherjee
Ruthenium (Ru) complexes are known for their promising anticancer activity presumably due to octahedral coordination geometry, slow ligand exchange rate, the range of different oxidation states and target specificity. This review article summarizes the physicochemical processes which are responsible for the selectivity of Ru complexes toward cancer cells over the normal cells. Emphasis has been given on the activation mechanism of Ru(III) complex administered as a prodrug and then the release of active species in an acidic environment of cancer cell through normal or photo induced hydrolysis or ligand oxidation...
March 7, 2018: European Journal of Medicinal Chemistry
Hong-Jie Li, Dong-Sheng Gao, Yong-Tao Li, Yong-Sheng Wang, Hong-Ying Liu, Jun Zhao
Porcine epidemic diarrhea virus (PEDV), a member of the Coronaviridae family, causes acute diarrhea, vomiting, dehydration, and high mortality rates in neonatal piglets. Severe outbreaks of PEDV variants have re-emerged in Asia and North America since 2010, causing tremendous economic losses to the swine industry. The lack of effective therapeutic treatment promotes the research for new antivirals. Lithium chloride (LiCl) has been reported as a potential antiviral drug for certain viruses. In this study, the antiviral effect of LiCl on PEDV in Vero cells was evaluated...
March 5, 2018: Research in Veterinary Science
Steve Peigneur, Jan Tytgat
Venoms from marine and terrestrial animals (cone snails, scorpions, spiders, snakes, centipedes, cnidarian, etc.) can be seen as an untapped cocktail of biologically active compounds, being increasingly recognized as a new emerging source of peptide-based therapeutics.
March 16, 2018: Toxins
J Russell Hoverman, Marcus A Neubauer, Melissa Jameson, Jad E Hayes, Kathryn J Eagye, Mitra Abdullahpour, Wendy J Haydon, Maria Sipala, Amy Supraner, Michael A Kolodziej, Diana K Verrilli
PURPOSE: Reform of cancer care delivery seeks to control costs while improving quality. Texas Oncology collaborated with Aetna to conduct a payer-sponsored program that used evidence-based treatment pathways, a disease management call center, and an introduction to advance care planning to improve patient care and reduce total costs. METHODS: From June 1, 2013, to May 31, 2016, 746 Medicare Advantage patients with nine common cancer diagnoses were enrolled. Patients electing for patient support services were telephoned by oncology nurses who assessed symptoms and quality of life and introduced advance care planning...
March 16, 2018: Journal of Oncology Practice
Ana Trapero, Angela Pacitto, Vinayak Singh, Mohamad Sabbah, Anthony G Coyne, Valerie Mizrahi, Tom L Blundell, David B Ascher, Chris Abell
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5´-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible (Mth) IMPDH(ΔCBS) inhibitors identified a low affinity phenylimidazole derivative...
March 16, 2018: Journal of Medicinal Chemistry
Kresimir Radic, Marko Curkovic, Dario Bagaric, Maja Vilibic, Andrea Tomic, Maja Zivkovic
Patients with schizophrenia, nowadays chronic, frequently disabling mental disorder, get initial treatment after detection of a psychotic episode, seemingly late, potentially preventable stage of illness. As our knowledge about the nature of schizophrenia and other diseases of the spectrum is growing, so are the early interventions becoming more possible, and it is important to conceptualize the clinical, legal and moral issues emerging with new preventive treatments. Every intervention, especially in pre-clinical population, demands a careful risk-benefit assessment and having basic bioethical principles - primacy of patient's welfare, beneficience/non-maleficience, autonomy and justice - in mind...
March 2018: Psychiatria Danubina
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
March 15, 2018: Drugs & Aging
Rishibha Sachdev, Karin Kappes-Horn, Lydia Paulsen, Yvonne Duernberger, Catharina Pleschka, Philip Denner, Bishwajit Kundu, Jens Reimann, Ina Vorberg
Sporadic inclusion body myositis (sIBM) is the most prevalent acquired muscle disorder in the elderly with no defined etiology or effective therapy. Endoplasmic reticulum stress and deposition of myostatin, a secreted negative regulator of muscle growth, have been implicated in disease pathology. The myostatin signaling pathway has emerged as a major target for symptomatic treatment of muscle atrophy. Here, we systematically analyzed the maturation and secretion of myostatin precursor MstnPP and its metabolites in a human muscle cell line...
March 15, 2018: Molecular Neurobiology
Beatriz V R Pereira, Gregorio Nolazco Matus, Monica Jones Costa, André Cordeiro Alves Dos Santos, Elaine C M Silva-Zacarin, Janaina Braga do Carmo, Bruno Nunes
Over time, many pollutants of anthropogenic origin have caused the contamination of aquatic ecosystems. Among several characteristics, these compounds can reach the trophic chain, causing deleterious interactions with the biota. Pharmaceutical substances can be included in this scenario as emerging contaminants that reach the aquatic environment because of direct human and veterinary usage, and release by industrial effluents, as well as through domestic dumping of surplus drugs. The effects of these compounds on exposed organisms have been studied since the 1990s, but ecotoxicological data for such chemicals are still scarce especially concerning aquatic organisms from tropical regions...
March 15, 2018: Environmental Science and Pollution Research International
Caterina Musolino, Giacomo Oteri, Alessandro Allegra, Manuela Mania, Angela D'Ascola, Angela Avenoso, Vanessa Innao, Andrea Gaetano Allegra, Salvatore Campo
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ...
March 15, 2018: Annals of Hematology
Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Ken Matsui, Makoto Ozawa, Maki Kiso, Makoto Yamashita, Toshihiko Maekawa, Minoru Kubota, Sumio Sugano, Yoshihiro Kawaoka
Influenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro...
March 15, 2018: Scientific Reports
Xueying Wang, Ksenia V Kastanenka, Michal Arbel-Ornath, Caitlin Commins, Akira Kuzuya, Amanda J Lariviere, Grant A Krafft, Franz Hefti, Jasna Jerecic, Brian J Bacskai
Soluble amyloid β oligomers (AβOs) are widely recognized neurotoxins that trigger aberrant signaling in specific subsets of neurons, leading to accumulated neuronal damage and memory disorders in Alzheimer's disease (AD). One of the profound downstream consequences of AβO-triggered events is dysregulation of cytosolic calcium concentration ([Ca2+ ]i ), which has been implicated in synaptic failure, cytoskeletal abnormalities, and eventually neuronal death. We have developed an in vitro/in vivo drug screening assay to evaluate putative AβO-blocking candidates by measuring AβO-induced real-time changes in [Ca2+ ]i ...
March 15, 2018: Scientific Reports
Jiantao Zhang, Yanmei Hu, Christopher Foley, Yuanxiang Wang, Rami Musharrafieh, Shuting Xu, Yongtao Zhang, Chunlong Ma, Christopher Hulme, Jun Wang
Influenza viruses are respiratory pathogens that are responsible for seasonal influenza and sporadic influenza pandemic. The therapeutic efficacy of current influenza vaccines and small molecule antiviral drugs is limited due to the emergence of multidrug-resistant influenza viruses. In response to the urgent need for the next generation of influenza antivirals, we utilized a fast-track drug discovery platform by exploring multi-component reaction products for antiviral drug candidates. Specifically, molecular docking was applied to screen a small molecule library derived from the Ugi-azide four-component reaction methodology for inhibitors that target the influenza polymerase PAC -PB1N interactions...
March 15, 2018: Scientific Reports
Aida Siyahian, Saad Ullah Malik, Adeela Mushtaq, Carol L Howe, Aneela Majeed, Tirdad Zangeneh, Samar Iftikhar, Shahid Habib, Umar Zahid, Irbaz Bin Riaz, Zabih Warraich, Warda Faridi, Faiz Anwer
Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug resistant strains. With the availability of newer antiviral agents like Entecavir, Telbivudine, Adefovir and Tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of seven databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials...
March 12, 2018: Biology of Blood and Marrow Transplantation
Chanjuan Wang, Aiwei Li, Shuo Yang, Rui Qiao, Xi Zhu, Jie Zhang
The emergence of chemoresistance greatly increases the recurrence risk for non-muscle invasive bladder cancer (NMIBC) patients, which is still a big concern of clinicians. Understanding the mechanisms of drug resistance is of great significance for preventing and reversing it. We showed here that CXC motif chemokine ligand 5 (CXCL5) was overexpressed in mitomycin C-resistant bladder cancer cell line M-RT4. Meanwhile, parental RT4 cell treated with recombinant human CXCL5 (rhCXCL5) reduced its sensitivity to mitomycin C...
March 12, 2018: Biochemical and Biophysical Research Communications
Julio Sandoval
Despite advances in drug therapy, pulmonary hypertension-particularly arterial hypertension (PAH)-remains a fatal disease. Untreatable right heart failure (RHF) from PAH eventually ensues and remains a significant cause of death in these patients. Lowering pulmonary input impedance with different PAH-specific drugs is the obvious therapeutic target in RHF due to chronically increased afterload. However, potential clinical gain can also be expected from attempts to unload the right heart and increase systemic output...
March 12, 2018: Revista Española de Cardiología
Swetha Sangomla, Mohd Aslam Saifi, Amit Khurana, Chandraiah Godugu
Doxorubicin (DOX) is one of the most commonly used anticancer drugs but its use has been limited due to constraints of cardiotoxic side effects. The precise mechanism underlying cardiotoxicity is not yet fully understood but oxidative stress has been found to be a primary mechanism behind this. In addition, DOX induced cardiotoxicity also shows involvement of proinflammatory cytokines such as IL-6 and TNF-α. Since oxidative stress plays major role in DOX induced cardiotoxicity, different antioxidants have been tried to prevent cardiotoxicity of DOX...
May 2018: Journal of Trace Elements in Medicine and Biology
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