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https://www.readbyqxmd.com/read/29779119/a-chemosensitizer-drug-disulfiram-prevents-doxorubicin-induced-cardiac-dysfunction-and-oxidative-stress-in-rats
#1
Varsha K Sonawane, Umesh B Mahajan, Sachin D Shinde, Subhajit Chatterjee, Sandip S Chaudhari, Harshada A Bhangale, Shreesh Ojha, Sameer N Goyal, Chanakya N Kundu, Chandragouda R Patil
In the present study, the preventive effects of orally administered disulfiram (DS) against the doxorubicin (DOX)-induced cardiotoxicity were investigated in rats. DS was orally administered for 7 days at doses of 2, 10, and 50 mg/kg/day. DOX (30 mg/kg) was intraperitoneally administered on the 5th day of the initiation of DS treatment. Within 48 h of injection, DOX treatment significantly altered ECG, elevated the ST height, and increased the QT and QRS intervals. It reduced the cardiac levels of injury markers like creatine kinase isoenzyme-MB and lactate dehydrogenase...
May 10, 2018: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29775474/the-cryptococcus-neoformans-titan-cell-is-an-inducible-and-regulated-morphotype-underlying-pathogenesis
#2
Ivy M Dambuza, Thomas Drake, Ambre Chapuis, Xin Zhou, Joao Correia, Leanne Taylor-Smith, Nathalie LeGrave, Tim Rasmussen, Matthew C Fisher, Tihana Bicanic, Thomas S Harrison, Marcel Jaspars, Robin C May, Gordon D Brown, Raif Yuecel, Donna M MacCallum, Elizabeth R Ballou
Fungal cells change shape in response to environmental stimuli, and these morphogenic transitions drive pathogenesis and niche adaptation. For example, dimorphic fungi switch between yeast and hyphae in response to changing temperature. The basidiomycete Cryptococcus neoformans undergoes an unusual morphogenetic transition in the host lung from haploid yeast to large, highly polyploid cells termed Titan cells. Titan cells influence fungal interaction with host cells, including through increased drug resistance, altered cell size, and altered Pathogen Associated Molecular Pattern exposure...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29775445/the-clinical-pattern-of-nephrotic-syndrome-in-children-has-no-effect-on-the-concentration-of-soluble-urokinase-receptor-supar-in-serum-and-urine
#3
Agnieszka Ochocińska, Wioletta Jarmużek, Roman Janas
Concentration of soluble urokinase receptor (suPAR) was regarded as viable marker to differentiate the focal segmental glomerulosclerosis (FSGS) from other glomerulopathies and also as predictive parameter for progression of renal disease. AIM: The aim of this study was to evaluate serum and urine (s)(u)suPAR concentration in steroid-sensitive and steroid-resistant nephrotic children treated with different (double and triple-drug) regimens. MATERIALS AND METHODS: Overall 43 children were evaluated including 14 patients with steroid-resistant nephrotic syndrome (SRNS) aged 9±6 years and 29 with steroid-sensitive nephrotic syndrome (SSNS) aged 9±5 years, as well as control group (n=59)...
April 23, 2018: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29774027/clinical-remission-of-sight-threatening-non-infectious-uveitis-is-characterized-by-an-upregulation-of-peripheral-t-regulatory-cell-polarized-towards-t-bet-and-tigit
#4
Rose M Gilbert, Xiaozhe Zhang, Robert D Sampson, Michael R Ehrenstein, Dao X Nguyen, Mahid Chaudhry, Charles Mein, Nadiya Mahmud, Grazyna Galatowicz, Oren Tomkins-Netzer, Virginia L Calder, Sue Lightman
Background: Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+ CD25+ FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772478/bacillus-thuringiensis-cry5b-protein-as-a-new-pan-hookworm-cure
#5
Yan Hu, Thanh-Thanh Nguyen, Alice C Y Lee, Joseph F Urban, Melanie M Miller, Bin Zhan, David J Koch, Jason B Noon, Ambily Abraham, Ricardo Toshio Fujiwara, Dwight D Bowman, Gary R Ostroff, Raffi V Aroian
Hookworms are intestinal nematode parasites that infect nearly half a billion people and are globally one of the most important contributors to iron-deficiency anemia. These parasites have significant impacts in developing children, pregnant women and working adults. Of all the soil-transmitted helminths or nematodes (STNs), hookworms are by far the most important, with disease burdens conservatively estimated at four million DALYs (Disability-Adjusted Life Years) and with productivity losses of up to US$139 billion annually...
May 4, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29772457/in-vitro-and-in-vivo-metabolic-investigation-of-the-palbociclib-by-uhplc-q-tof-ms-ms-and-in-silico-toxicity-studies-of-its-metabolites
#6
Balasaheb B Chavan, Shristy Tiwari, Shankar G, Rakesh D Nimbalkar, Prabha Garg, Srinivas R, M V N Kumar Talluri
Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug...
May 14, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#7
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29771932/a-multi-center-preclinical-study-of-gadoxetate-dce-mri-in-rats-as-a-biomarker-of-drug-induced-inhibition-of-liver-transporter-function
#8
Anastassia Karageorgis, Stephen C Lenhard, Brittany Yerby, Mikael F Forsgren, Serguei Liachenko, Edvin Johansson, Mark A Pilling, Richard A Peterson, Xi Yang, Dominic P Williams, Sharon E Ungersma, Ryan E Morgan, Kim L R Brouwer, Beat M Jucker, Paul D Hockings
Drug-induced liver injury (DILI) is a leading cause of acute liver failure and transplantation. DILI can be the result of impaired hepatobiliary transporters, with altered bile formation, flow, and subsequent cholestasis. We used gadoxetate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), combined with pharmacokinetic modelling, to measure hepatobiliary transporter function in vivo in rats. The sensitivity and robustness of the method was tested by evaluating the effect of a clinical dose of the antibiotic rifampicin in four different preclinical imaging centers...
2018: PloS One
https://www.readbyqxmd.com/read/29770096/canadian-recommendations-for-laboratory-interpretation-of-multiple-or-extensive-drug-resistance-in-clinical-isolates-of-enterobacteriaceae-acinetobacter-species-and-pseudomonas-aeruginosa
#9
G J German, M Gilmour, G Tipples, H J Adam, H Almohri, J Bullard, T Dingle, D Farrell, G Girouard, D Haldane, L Hoang, P N Levett, R Melano, J Minion, R Needle, S N Patel, R Rennie, R C Reyes, J Longtin, M R Mulvey
The goal of this document was to provide Canadian laboratories with a framework for consistent reporting and monitoring of multidrug resistant organisms (MDRO) and extensively drug resistant organisms (XDRO) for common gram-negative pathogens. This is the final edition of the interim recommendations, which were modified after one year of broad consultative review. This edition represents a consensus of peer-reviewed information and was co-authored by the Canadian Public Health Laboratory Network and the Canadian Association of Clinical Microbiology and Infectious Diseases...
January 4, 2018: Canada Communicable Disease Report, Relevé des Maladies Transmissibles Au Canada
https://www.readbyqxmd.com/read/29769321/lectin-mediated-binding-and-sialoglycans-of-porcine-surfactant-protein-d-synergistically-neutralize-influenza-a-virus
#10
Martin van Eijk, Michael J Rynkiewicz, Kshitij Khatri, Nancy Leymarie, Joseph Zaia, Mitchell R White, Kevan L Hartshorn, Tanya R Cafarella, Irma Van Die, Martin Hessing, Barbara A Seaton, Henk P Haagsman
Innate immunity is critical in the early containment of influenza A virus (IAV) infection, and surfactant protein D (SP-D) plays a crucial role in the pulmonary defense against IAV. In pigs, which are important intermediate hosts during the generation of pandemic IAVs, SP-D uses its unique carbohydrate recognition domain (CRD) to interact with IAV. An N-linked CRD-glycosylation provides interactions with the sialic acid binding site of IAV, and a tripeptide loop at the lectin binding site facilitates enhanced interactions with IAV glycans...
May 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29769246/small-molecule-positive-allosteric-modulators-of-the-%C3%AE-2-adrenoceptor-isolated-from-dna-encoded-libraries
#11
Seungkirl Ahn, Biswaranjan Pani, Alem W Kahsai, Eva K Olsen, Gitte Husemoen, Mikkel Vestrgaard, Lei Jin, Shuai Zhao, Laura M Wingler, Paula K Rambarat, Rishabh K Simhal, Thomas T Xu, Lillian D Sun, Paul J Shim, Dean P Staus, Li-Yin Huang, Thomas Franch, Xin Chen, Robert J Lefkowitz
Conventional drug discovery efforts at the β2 -adrenoceptor (β2 AR) have led to the development of ligands that bind almost exclusively to the receptor's hormone-binding orthosteric site. However, targeting the largely unexplored and evolutionarily unique allosteric sites has potential for developing more specific drugs with fewer side effects than orthosteric ligands. Using our recently developed approach for screening G protein-coupled receptors (GPCRs) with DNA-encoded small molecule libraries, we have discovered and characterized the first β2 AR small molecule positive allosteric modulators (PAMs) - compound-6 [(R)-N-(4-amino-1-(4-(tert-butyl)phenyl)-4-oxobutan-2-yl)-5-(N-isopropyl-N-methylsulfamoyl)-2-((4-methoxyphenyl) thio)benzamide] and its analogs...
May 16, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29769160/cross-border-outbreak-of-extensively-drug-resistant-tuberculosis-linked-to-a-university-in-romania
#12
O Popovici, Ph Monk, D Chemtob, D Chiotan, P J Freidlin, R Groenheit, M Haanperä, D Homorodean, M Mansjö, E Robinson, E Rorman, G Smith, H Soini, M J Van Der Werf
Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases...
May 2018: Epidemiology and Infection
https://www.readbyqxmd.com/read/29768629/controversial-issues-in-the-management-of-hyperprolactinemia-and-prolactinomas-an-overview-by-the-neuroendocrinology-department-of-the-brazilian-society-of-endocrinology-and-metabolism
#13
Lucio Vilar, Julio Abucham, José Luciano Albuquerque, Luiz Antônio Araujo, Monalisa F Azevedo, Cesar Luiz Boguszewski, Luiz Augusto Casulari, Malebranche B C Cunha Neto, Mauro A Czepielewski, Felipe H G Duarte, Manuel Dos S Faria, Monica R Gadelha, Heraldo M Garmes, Andrea Glezer, Maria Helane Gurgel, Raquel S Jallad, Manoel Martins, Paulo A C Miranda, Renan M Montenegro, Nina R C Musolino, Luciana A Naves, Antônio Ribeiro-Oliveira Júnior, Cíntia M S Silva, Camila Viecceli, Marcello D Bronstein
Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare...
March 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29768576/recent-advances-and-perspectives-in-cancer-drug-design
#14
Luma G Magalhaes, Leonardo L G Ferreira, Adriano D Andricopulo
Cancer is one of the leading causes of death worldwide. With the increase in life expectancy, the number of cancer cases has reached unprecedented levels. In this scenario, the pharmaceutical industry has made significant investments in this therapeutic area. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments...
May 14, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29768236/rapid-synthesis-of-bi-2-o-3-nano-needles-via-green-route-and-evaluation-of-its-anti-fungal-activity
#15
Abhishek R Indurkar, Viraj D Sangoi, Prashant B Patil, Mansingraj S Nimbalkar
Here, the authors report a rapid, simple, and eco-friendly process for synthesis of Bi2 O3 nano-needles. Dioscorea alata tuber extract was used as both reducing and capping agent for the first time. These nanoparticles were characterised by X-ray diffraction, field emission scanning electron microscope, and Fourier transform infrared (FTIR) spectrometry, the nano-structured Bi2 O3 needles have an average diameter of 158 nm with the lengths in the range of 1-3 μm. CLSI M27-A2 standard was followed for evaluation of anti-fungal activity...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29767688/safety-and-dose-modification-for-patients-receiving-niraparib
#16
J S Berek, U A Matulonis, U Peen, P Ghatage, S Mahner, A Redondo, A Lesoin, N Colombo, I Vergote, O Rosengarten, J Ledermann, M Pineda, S Ellard, J Sehouli, A Gonzalez-Martin, D Berton-Rigaud, R Madry, A Reinthaller, S Hazard, W Guo, M R Mirza
Background: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions...
May 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29766820/salient-aspects-of-pbp2a-inhibition-a-qsar-study
#17
Adewale J Ogunleye, Gabriel O Eniafe, Olumide K Inyang, Benjamin Adewumi, Olaposi I Omotuyi
Backgound: Inhibition of penicillin binding protein 2A (PBP2A) represents a sound drug design strategy in combatting Methicillin resistant Staphylococcus aureus (MRSA). Considering the urgent need for effective antimicrobials in combatting MRSA infections, we have developed a statistically robust ensemble of molecular descriptors (1, 2, & 3-D) from compounds targeting PBP2A in vivo. METHODS: 37 (training set: 26, test set: 11) PBP2A-inhibitors were submitted for descriptor generation after which an unsupervised, non-exhaustive genetic algorithm (GA) was deployed for fishing out the best descriptor subset...
May 15, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29766504/indene-compounds-synthetically-derived-from-vitamin-d-have-selective-antibacterial-action-on-helicobacter-pylori
#18
Kiyofumi Wanibuchi, Kouichi Hosoda, Masato Ihara, Kentaro Tajiri, Yuki Sakai, Hisashi Masui, Takashi Takahashi, Yoshikazu Hirai, Hirofumi Shimomura
Helicobacter pylori infects the human stomach and is closely linked with the development of gastric cancer. When detected, this pathogen can be eradicated from the human stomach using wide-spectrum antibiotics. However, year by year, H. pylori strains resistant to the antibacterial action of antibiotics have been increasing. The development of new antibacterial substances effective against drug-resistant H. pylori is urgently required. Our group has recently identified extremely selective bactericidal effects against H...
May 16, 2018: Lipids
https://www.readbyqxmd.com/read/29766045/post-stroke-intranasal-naloxone-delivery-reduces-microglial-activation-and-improves-behavioral-recovery-from-ischemic-injury
#19
Jenni E Anttila, Katrina Albert, Emily S Wires, Kert Mätlik, Lisa C Loram, Linda R Watkins, Kenner C Rice, Yun Wang, Brandon K Harvey, Mikko Airavaara
Ischemic stroke is the leading cause of disability, and effective therapeutic strategies are needed to promote complete recovery. Neuroinflammation plays a significant role in stroke pathophysiology, and there is limited understanding of how it affects recovery. The aim of this study was to characterize the spatiotemporal expression profile of microglial activation and whether dampening microglial/macrophage activation post-stroke facilitates the recovery. For dampening microglial/macrophage activation, we chose intranasal administration of naloxone, a drug that is already in clinical use for opioid overdose and is known to decrease microglia/macrophage activation...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29764522/treatment-resistant-depression-and-peripheral-c-reactive-protein
#20
Samuel R Chamberlain, Jonathan Cavanagh, Peter de Boer, Valeria Mondelli, Declan N C Jones, Wayne C Drevets, Philip J Cowen, Neil A Harrison, Linda Pointon, Carmine M Pariante, Edward T Bullmore
BACKGROUND: C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.AimTo explore CRP in MDD and its phenotypic associations. METHOD: We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers...
May 16, 2018: British Journal of Psychiatry: the Journal of Mental Science
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