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https://www.readbyqxmd.com/read/29662636/analysis-of-hematological-parameters-as-prognostic-markers-for-toxicity-and-survival-of-223-radium-treatment
#1
Asha Leisser, Marzieh Nejabat, Markus Hartenbach, Reza Agha Mohammadi Sareshgi, Shahrokh Shariat, Gero Kramer, Michael Krainer, Marcus Hacker, Alexander R Haug
223 Radium (223 Ra) has emerged as treatment prolonging survival in patients with metastatic castration-resistant prostate cancer (CRPC). As 223 Ra can cause hematotoxicity (HT), pre-existing hematopoiesis might influence the efficacy of 223 Ra and the rate of hematotoxicity, but as to our knowledge such data has not been published yet, we retrospectively conducted an analysis on patients receiving 223 Ra. 54 patients treated with 223 Ra had a median survival of 67 weeks, which was significantly reduced in patients with pre-existing Hb toxicity (Tox) grade 2 (48 weeks P = 0...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29655693/molecular-modeling-and-in-vitro-approaches-towards-cholinesterase-inhibitory-effect-of-some-natural-xanthohumol-naringenin-and-acyl-phloroglucinol-derivatives
#2
Ilkay Erdogan Orhan, Dariusz Jedrejek, F Sezer Senol, Ramin Ekhteiari Salmas, Serdar Durdagi, Iwona Kowalska, Lukasz Pecio, Wieslaw Oleszek
BACKGROUND: Many natural products, particularly phenolic compounds, have been reported to have a strong inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the key enzymes in the pathology of Alzheimer's disease (AD). HYPOTHESIS: Therefore, we hypothesized that some xanthahumol, naringenin, and acyl phloroglucinol derivatives (1-14) isolated from Humulus lupulus L. (hops) may have an inhibitory potential against AChE and BChE. METHODS: Inhibitory potential of compounds 1-14 were tested against AChE and BChE using ELISA microtiter assay...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29618901/-agemone-mexicana-flavanones-apposite-inverse-agonists-of-the-%C3%AE-2-adrenergic-receptor-in-asthma-treatment
#3
Gabriel O Eniafe, Damilohun S Metibemu, Olaposi I Omotuyi, Adewale J Ogunleye, Olumide K Inyang, Niyi S Adelakun, Yakubu O Adeniran, Bamidele Adewumi, Ojochenemi A Enejoh, Joseph O Osunmuyiwa, Sidiqat A Shodehinde, Oluwatoba E Oyeneyin
Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs. The synthetic agonists of the β2-adrenergic receptor used over the years proved effective, but with indispensable side effects, thereby limiting their therapeutic use on a long-term scale. Inverse agonists of this receptor, although initially contraindicated, had been reported to have long-term beneficial effects...
2018: Bioinformation
https://www.readbyqxmd.com/read/29616106/data-mining-of-pediatric-medulloblastoma-microarray-expression-reveals-a-novel-potential-subdivision-of-the-group-4-molecular-subgroup
#4
Rosa Angélica Castillo-Rodríguez, Víctor Manuel Dávila-Borja, Sergio Juárez-Méndez
Medulloblastoma is the most common type of solid brain tumor in children. This type of embryonic tumor is highly heterogeneous and has been classified into 4 molecular subgroups based on their gene expression profiles: WNT, SHH, Group 3 (G3) and Group 4 (G4). WNT and SHH tumors exhibit the specific dysregulation of genes and pathways, whereas G3 and G4 tumors, two of the more frequent subtypes, are the least characterized. Thus, novel markers to aid in the diagnosis, prognosis and management of medulloblastoma are required...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29578175/tox-high-mobility-group-box-family-member-3-rs3803662-and-breast-cancer-risk-a-meta-analysis
#5
Lin Li, Guangcheng Guo, Fang Wang, Pengwei Lv, Mingzhi Zhu, Yuanting Gu, Mingli Han, Xinhong Pei
Aims: Some studies suggested that TOX high mobility group box family member 3 (TOX3) rs3803662 polymorphism was associated with the risk of breast cancer. However, the results were controversy. Therefore, in order to derive a more comprehensive estimation of the association between TOX3 rs3803662 polymorphism and breast cancer risk, we conducted a meta-analysis to investigate this relationship. Materials and Methods: An electronic literature search was conducted using the following database: PubMed, EMBASE, and China National Knowledge Infrastructure till to March 31, 2015...
2018: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29574388/formation-of-dbps-and-halogen-specific-tox-in-the-presence-of-iopamidol-and-chlorinated-oxidants
#6
Nana Osei B Ackerson, Edward J Machek, Alexis H Killinger, Elizabeth A Crafton, Pushpita Kumkum, Hannah K Liberatore, Michael J Plewa, Susan D Richardson, Thomas A Ternes, Stephen E Duirk
Iopamidol is a known direct precursor to iodinated and chlorinated DBP formation; however, the influence of iopamidol on both iodo/chloro-DBP formation has yet to be fully investigated. This study investigated the effect of iopamidol on the formation and speciation of halogen-specific total organic halogen (TOX), as well as iodo/chloro-DBPs, in the presence of 3 source waters (SWs) from Northeast Ohio and chlorinated oxidants. Chlorination and chloramination of SWs were carried out at pH 6.5-9.0 and, different iopamidol and dissolved organic carbon (DOC) concentrations...
March 16, 2018: Chemosphere
https://www.readbyqxmd.com/read/29549837/design-synthesis-biological-evaluation-and-in-vivo-testing-of-dual-phosphodiesterase-5-pde5-and-histone-deacetylase-6-hdac6-selective-inhibitors-for-the-treatment-of-alzheimer-s-disease
#7
Obdulia Rabal, Juan A Sánchez-Arias, Mar Cuadrado-Tejedor, Irene de Miguel, Marta Pérez-González, Carolina García-Barroso, Ana Ugarte, Ander Estella-Hermoso de Mendoza, Elena Sáez, Maria Espelosin, Susana Ursua, Tan Haizhong, Wu Wei, Xu Musheng, Ana Garcia-Osta, Julen Oyarzabal
We have identified chemical probes that act as dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors (>1 log unit difference versus class I HDACs) to decipher the contribution of HDAC isoforms to the positive impact of dual-acting PDE5 and HDAC inhibitors on mouse models of Alzheimer's disease (AD) and fine-tune this systems therapeutics approach. Structure- and knowledge-based approaches led to the design of first-in-class molecules with the desired target compound profile: dual PDE5 and HDAC6-selective inhibitors...
March 14, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29523087/changes-in-mlst-profiles-and-biotypes-of-corynebacterium-diphtheriae-isolates-from-the-diphtheria-outbreak-period-to-the-period-of-invasive-infections-caused-by-nontoxigenic-strains-in-poland-1950-2016
#8
Urszula Czajka, Aldona Wiatrzyk, Ewa Mosiej, Kamila Formińska, Aleksandra A Zasada
BACKGROUND: Corynebacterium diphtheriae is a re-emerging pathogen in Europe causing invasive infections in vaccinated persons and classical diphtheria in unvaccinated persons. In the presented study we analysed genetic changes in C. diphtheriae isolates collected in Poland from the period before the introduction of the mass anti-diphtheria vaccination to the present time when over 98% of the population is vaccinated. METHODS: A total of 62 C. diphtheriae isolates collected in the 1950s-1960s, 1990s and 2000-2016 in Poland were investigated...
March 9, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29497406/detection-and-characterization-of-enteropathogenic-and-shiga-toxin-producing-escherichia-coli-strains-in-rattus-spp-from-buenos-aires
#9
Ximena Blanco Crivelli, María P Bonino, Paula Von Wernich Castillo, Armando Navarro, Osvaldo Degregorio, Adriana Bentancor
Enteropathogenic Escherichia coli (EPEC) and Shiga toxin-producing E. coli (STEC) are pathovars of E. coli that impact human health by causing childhood diseases. In this work, 118 synanthropic rodents of the genus Rattus from Buenos Aires, Argentina were evaluated as EPEC and STEC carriers. Rectal swab samples from captured animals were evaluated by conventional PCR to detect the presence of the eae , stx 1, stx 2, and rfb O157 genes. Twenty-one isolates were obtained (17 EPEC isolates from seven animals and four STEC isolates from the same animal)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29493425/pharmacophore-and-structure-based-drug-design-molecular-dynamics-and-admet-tox-studies-to-design-novel-potential-pad4-inhibitors
#10
Mariana P Barcellos, Cleydson B R Santos, Leonardo B Federico, Paulo Fernando de Almeida, Carlos H T P da Silva, Carlton A Taft
We have used docking (GLIDE), pharmacophore modeling (Discovery Studio), long trajectory molecular dynamics (Discovery Studio) and ADMET/Tox (QikProp and DEREK) to investigate PAD4 in order to determine potential novel inhibitors and hits. We have carried out virtual screening in the ZINC natural compounds database. Pharmacokinetics and Toxicity of the best hits were assessed using databases implemented in softwares that create models based on chemical structures taking into account consideration about the toxicophoric groups...
March 1, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29457584/immunological-stability-of-clostridium-difficile-toxins-in-clinical-specimens
#11
Donna M Schora, Lance R Peterson, Elena A Usacheva
OBJECTIVE The impact of storage on stability and detection of Clostridium difficile toxins in feces is poorly understood. The objective of this study was to investigate the immunological stability of C. difficile toxins in clinical stool specimens under different storage conditions by evaluating this stability using toxin detection by enzyme immunoassay (EIA). METHODS Stool specimens positive for C. difficile infection (CDI) by quantitative polymerase chain reaction (qPCR) were used for EIA testing with the C...
February 19, 2018: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/29454806/oxidative-imbalance-in-mice-intoxicated-by-microcystin-lr-can-be-minimized
#12
Natália V Casquilho, Maria Diana Moreira-Gomes, Clarissa B Magalhães, Renata T Okuro, Victor Hugo Ortenzi, Emanuel K Feitosa-Lima, Lidia M Lima, Eliezer J Barreiro, Raquel M Soares, Sandra M F O Azevedo, Samuel S Valença, Rodrigo S Fortunato, Alysson Roncally Carvalho, Walter A Zin
Microcystins-LR (MC-LR) is a cyanotoxin produced by cyanobacteria. We evaluated the antioxidant potential of LASSBio-596 (LB-596, inhibitor of phosphodiesterases 4 and 5), per os, and biochemical markers involved in lung and liver injury induced by exposure to sublethal dose of MC-LR. Fifty male Swiss mice received an intraperitoneal injection of 60 μL of saline (CTRL group, n = 20) or a sublethal dose of MC-LR (40 μg/kg, TOX group, n = 20). After 6 h the animals received either saline (TOX and CTRL groups) or LB-596 (50 mg/kg, TOX + LASS group, n = 10) by gavage...
February 15, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29454190/potholing-of-the-hydrophobic-heme-oxygenase-1-western-region-for-the-search-of-potent-and-selective-imidazole-based-inhibitors
#13
Loredana Salerno, Emanuele Amata, Giuseppe Romeo, Agostino Marrazzo, Orazio Prezzavento, Giuseppe Floresta, Valeria Sorrenti, Ignazio Barbagallo, Antonio Rescifina, Valeria Pittalà
Here we report the design, synthesis, and molecular modeling of new potent and selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested compounds showed a good inhibitor activity with IC 50 values in the low micromolar range, with two of them (1b and 1j) exhibiting also high selectivity toward HO-2. These results were obtained by the idea of potholing the entire volume of the principal hydrophobic western region with an appropriate ligand volume...
February 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29451361/development-of-a-focused-library-of-triazole-linked-privileged-structure-based-conjugates-leading-to-the-discovery-of-novel-phenotypic-hits-against-protozoan-parasitic-infections
#14
Elisa Uliassi, Lorna Piazzi, Federica Belluti, Andrea Mazzanti, Marcel Kaiser, Reto Brun, Carolina B Moraes, Lucio H Freitas-Junior, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Chiara Borsari, Maria Paola Costi, Maria Laura Bolognesi
Protozoan infections caused by Plasmodium, Leishmania, and Trypanosoma spp. contribute significantly to the burden of infectious diseases worldwide, causing severe morbidity and mortality. The inadequacy of available treatments calls for cost- and time-effective drug discovery endeavors. To this end, we envisaged the triazole linkage of privileged structures as an effective drug design strategy to generate a focused library of high-quality compounds. The versatility of this approach was combined with the feasibility of a phenotypic assay, integrated with early ADME-tox profiling...
February 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29404794/computational-assessment-of-pharmacokinetics-and-biological-effects-of-some-anabolic-and-androgen-steroids
#15
Marin Roman, Diana Larisa Roman, Vasile Ostafe, Alecu Ciorsac, Adriana Isvoran
PURPOSE: The aim of this study is to use computational approaches to predict the ADME-Tox profiles, pharmacokinetics, molecular targets, biological activity spectra and side/toxic effects of 31 anabolic and androgen steroids in humans. METHODS: The following computational tools are used: (i) FAFDrugs4, SwissADME and admetSARfor obtaining the ADME-Tox profiles and for predicting pharmacokinetics;(ii) SwissTargetPrediction and PASS online for predicting the molecular targets and biological activities; (iii) PASS online, Toxtree, admetSAR and Endocrine Disruptomefor envisaging the specific toxicities; (iv) SwissDock to assess the interactions of investigated steroids with cytochromes involved in drugs metabolism...
February 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29398302/organs-on-a-chip-current-applications-and-consideration-points-for-in%C3%A2-vitro-adme-tox-studies
#16
REVIEW
Seiichi Ishida
Assay systems using in vitro cultured cells are increasingly applied for evaluation of the efficacy, safety, and toxicity of drug candidates. In vitro cell-based assays have two main applications in the drug discovery process: searching for a compound that is effective against the target disease (seed investigation) and confirmation of safety during use of the identified compounds (safety assessment). Currently available in vitro cell-based assays have been designed to evaluate the efficacy and toxicity in single organs, but the in vivo pharmacokinetics and pharmacodynamics of the administered drug candidates have not been considered...
January 11, 2018: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29390151/high-co2-hypoxia-responsive-transcription-factor-network-involved-in-persimmon-fruit-deastringency
#17
Qing-Gang Zhu, Zi-Yuan Gong, Miao-Miao Wang, Xian Li, Donald Grierson, Xue-Ren Yin, Kun-Song Chen
Plant responses to anaerobic environments are regulated by ethylene response factors (ERFs) in both vegetative and productive organs, but the roles of other transcription factors (TFs) in hypoxia responses are poorly understood. Here, eight TFs (DkbHLH1, DkMYB9/10/11, DkRH2-1, DkGT3-1, DkAN1-1, DkHSF1) were shown to be strongly up-regulated by AHCA (artificial high CO2 atmosphere, 1 % O2 and 95 % CO2). Dual-luciferase assay indicated some TFs were activators of previously characterized DkERFs, including DkMYB10 for the DkERF9 promoter, DkERF18/19 and DkMYB6 for the DkERF19 promoter, DkERF21/22 for the DkERF10 promoter...
January 30, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29376224/long-term-efficacy-of-botulinum-neurotoxin-a-treatment-for-essential-blepharospasm
#18
Seunghyun Lee, Sangrye Park, Helen Lew
PURPOSE: In the present study, we investigated the treatment efficacy and clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than 5 years to patients with essential blepharospasm. METHODS: We retrospectively reviewed 19 patients (male : female = 8 : 11) diagnosed with essential blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections for over 5 years and were followed. Efficacy of 297 injections of Botox (n = 162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on the symptom improvement score at the final injection (-1, worse; 0, same; 1, better)...
January 24, 2018: Korean Journal of Ophthalmology: KJO
https://www.readbyqxmd.com/read/29370758/transcriptome-sequencing-of-the-human-pathogen-corynebacterium-diphtheriae-nctc-13129-provides-detailed-insights-into-its-transcriptional-landscape-and-into-dtxr-mediated-transcriptional-regulation
#19
Manuel Wittchen, Tobias Busche, Andrew H Gaspar, Ju Huck Lee, Hung Ton-That, Jörn Kalinowski, Andreas Tauch
BACKGROUND: The human pathogen Corynebacterium diphtheriae is the causative agent of diphtheria. In the 1990s a large diphtheria outbreak in Eastern Europe was caused by the strain C. diphtheriae NCTC 13129. Although the genome was sequenced more than a decade ago, not much is known about its transcriptome. Our aim was to use transcriptome sequencing (RNA-Seq) to close this knowledge gap and gain insights into the transcriptional landscape of a C. diphtheriae tox+ strain. RESULTS: We applied two different RNA-Seq techniques, one to retrieve 5'-ends of primary transcripts and the other to characterize the whole transcriptional landscape in order to gain insights into various features of the C...
January 25, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29369159/substance-associated-elevations-in-monocyte-activation-among-methamphetamine-users-with-treated-hiv-infection
#20
Adam W Carrico, Emily M Cherenack, Margaret E Roach, Elise D Riley, Olorunleke Oni, Samantha E Dilworth, Steven Shoptaw, Peter Hunt, Sabita Roy, Suresh Pallikkuth, Savita Pahwa
OBJECTIVE: Microbial translocation and monocyte activation predict mortality in treated HIV. We examined whether substance use independently contributes to these pathophysiologic processes. DESIGN: Cross-sectional study at baseline for a randomized controlled trial. METHODS: HIV-positive, methamphetamine-using men who have sex with men (MSM) with undetectable HIV viral load (< 40 copies/mL) were enrolled. We examined if plasma biomarkers of monocyte activation and intestinal barrier integrity were associated with the following: 1) reactive urine toxicology results (Tox+) for stimulants (i...
January 23, 2018: AIDS
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