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https://www.readbyqxmd.com/read/29352735/s-nitrosated-poly-propylene-sulfide-nanoparticles-for-enhanced-nitric-oxide-delivery-to-lymphatic-tissues
#1
Alex Schudel, Lauren F Sestito, Susan N Thomas
Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases affecting lymphatic tissues, which range from infectious and cardiovascular diseases to cancer. Existing technologies available for NO therapy, however, provide poor bioactivity within lymphatic tissues. In this work, we address this technology gap with a NO encapsulation and delivery strategy leveraging the formation of S-nitrosothiols on lymphatic-targeting Pluronic-stabilized, poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the lymphatic versus systemic delivery of NO resulting from intradermal administration of SNO-NP benchmarked against a commonly used, commercially available small molecule S-nitrosothiol NO donor, examined signs of toxicity systemically as well as localized to the site of injection, and investigated SNO effects on lymphatic transport and NP uptake by LN-resident cells...
January 20, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29352727/re-evaluation-of-target-lipid-model-derived-hc5-predictions-for-hydrocarbons
#2
Joy A McGrath, Christopher J Fanelli, Dominic M Di Toro, Thomas F Parkerton, Aaron D Redman, Miriam Leon Paumen, Mike Comber, Charles V Eadsforth, Klaas den Haan
The Target Lipid Model (TLM) has been previously applied to predict the aquatic toxicity of hydrocarbons and other non-ionic organic chemicals and for deriving HC5 values, concentrations above which 95% of species should be protected. Several concerns were identified with the TLM-derived HC5 when applied in a substance risk assessment context. These shortcomings were addressed by expanding the acute and chronic toxicity databases to include more diverse taxonomic groups and increase the number of species. The TLM was recalibrated with these expanded databases resulting in critical target lipid body burdens and acute-to-chronic ratios that met the required guidelines for using species sensitivity distributions in substance risk assessment...
January 20, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29352714/effect-of-single-agent-daily-prednisone-on-outcomes-and-toxicities-in-metastatic-castration-resistant-prostate-cancer-pooled-analysis-of-prospective-studies
#3
REVIEW
Pooja Ghatalia, Gregory R Pond, Arnoud J Templeton, Guru Sonpavde
The clinical effect of prednisone in metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized controlled trials that had or had not administered single-agent prednisone. Randomized controlled trials with a control arm that included single-agent placebo (or no anticancer therapy) or single-agent prednisone (with or without placebo) were eligible for analysis. Patients receiving prednisone combined with other agents in the control arm were excluded...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29352640/recent-advancements-in-bioremediation-of-dye-current-status-and-challenges
#4
REVIEW
Kumar Vikrant, Balendu Shekhar Giri, Nadeem Raza, Kangkan Roy, Ki-Hyun Kim, Birendra Nath Rai, Ram Sharan Singh
The rampant industrialization and unchecked growth of modern textile production facilities coupled with the lack of proper treatment facilities have proliferated the discharge of effluents enriched with toxic, baleful, and carcinogenic pollutants including dyes, heavy metals, volatile organic compounds, odorants, and other hazardous materials. Therefore, the development of cost-effective and efficient control measures against such pollution is imperative to safeguard ecosystems and natural resources. In this regard, recent advances in biotechnology and microbiology have propelled bioremediation as a prospective alternative to traditional treatment methods...
January 8, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29352572/phase-i-combination-study-of-the-parp-inhibitor-veliparib-plus-carboplatin-and-gemcitabine-in-patients-with-advanced-ovarian-cancer-and-other-solid-malignancies
#5
Heidi J Gray, Katherine Bell-McGuinn, Gini F Fleming, Mihaela Cristea, Hao Xiong, Danielle Sullivan, Yan Luo, Mark D McKee, Wijith Munasinghe, Lainie P Martin
OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In this phase I study, patients with metastatic or unresectable solid tumors and ≤2 prior chemotherapy regimens received veliparib combined with carboplatin area under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21-day cycle for maximum 10cycles, followed by optional veliparib maintenance therapy...
January 15, 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29352516/successful-hematopoietic-cell-transplantation-following-cardiac-transplantation-in-two-pediatric-patients
#6
Rachel Phelan, Angela R Smith, Paul J Orchard, Rebecca K Ameduri
We report two patients who underwent cardiac transplantation at a young age and subsequently required a HCT for varied indications. Despite the challenges associated with HCT following cardiac transplant, including need for altered immunosuppression, toxicities related to chemotherapy exposure, and infection risks, both patients are currently alive and well. There is a paucity of such successful cases documented in the literature, and these cases highlight the critical importance of an experienced, multidisciplinary team when caring for this patient population...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352515/principles-of-alemtuzumab-immunoablation-in-hematopoietic-cell-transplantation-for-non-malignant-diseases-in-children-a-review
#7
REVIEW
Gregory M T Guilcher, Ravi Shah, Shalini Shenoy
Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non-malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable...
January 19, 2018: Pediatric Transplantation
https://www.readbyqxmd.com/read/29352450/carrier-mediated-uptake-of-clonidine-in-cultured-human-lung-cells
#8
Marc Le Vée, Elodie Jouan, Olivier Fardel
The lung is a preferential organ site for accumulation of lipophilic basic amine drugs, so-called pneumophilic drugs and belonging to various pharmacological classes, which can result in lung toxicity. In order to investigate the mechanism involved in such pulmonary accumulation of drugs, uptake of clonidine, used here as a prototypical basic amine drug, was characterized in cultured human lung cells. Clonidine accumulation in lung alveolar A549 cells was found to be temperature- and pH-dependent; it was saturable, with a Michaelis-Menten affinity constant (Km) value of 569...
January 19, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29352397/bio-prospectus-of-cadmium-bioadsorption-by-lactic-acid-bacteria-to-mitigate-health-and-environmental-impacts
#9
REVIEW
Narendra Kumar, Vandna Kumari, Chand Ram, Kiran Thakur, Sudhir Kumar Tomar
Foodstuffs and water are the key sources of cadmium biomagnifiaction. The available strategies to mitigate this problem are unproductive and expensive for practical large-scale use. Biological decontamination of metals through environmental microbes has been known since long time, whereas lactic acid bacteria (LAB) have not been extensively studied for this purpose. The LAB are known for maintaining homeostasis and suppression of pathogens in humans and animals. They also play a vital role in bioremediation of certain heavy metals...
January 19, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29352355/physiological-responses-to-salt-stress-of-salt-adapted-and-directly-salt-nacl-and-nacl-na2so4-mixture-stressed-cyanobacterium-anabaena-fertilissima
#10
Prashant Swapnil, Ashwani K Rai
Soil salinity in nature is generally mixed type; however, most of the studies on salt toxicity are performed with NaCl and little is known about sulfur type of salinity (Na2SO4). Present study discerns the physiologic mechanisms responsible for salt tolerance in salt-adapted Anabaena fertilissima, and responses of directly stressed parent cells to NaCl and NaCl+Na2SO4 mixture. NaCl at 500 mM was lethal to the cyanobacterium, whereas salt-adapted cells grew luxuriantly. Salinity impaired gross photosynthesis, electron transport activities, and respiration in parent cells, but not in the salt-adapted cells, except a marginal increase in PSI activity...
January 19, 2018: Protoplasma
https://www.readbyqxmd.com/read/29352318/temozolomide-induced-increase-of-tumorigenicity-can-be-diminished-by-targeting-of-mitochondria-in-in-vitro-models-of-patient-individual-glioblastoma
#11
Doreen William, Madlin Walther, Björn Schneider, Michael Linnebacher, Carl Friedrich Classen
Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain tumor with a dismal prognosis. Development of resistance towards cytostatic drugs like the GBM standard drug temozolomide is a severe problem in GBM treatment. One potential source of GBM relapse could be so called cancer stem like cells (CSCs). These represent an undifferentiated subpopulation of cells with high potential for tumor initiation. Furthermore, it has been shown that differentiated GBM cells can regain CSC properties when exposed to continuous temozolomide treatment in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29352267/differential-susceptibility-of-striatal-hippocampal-and-cortical-neurons-to-caspase-6
#12
Anastasia Noël, Libin Zhou, Bénédicte Foveau, P Jesper Sjöström, Andréa C LeBlanc
Active cysteinyl protease Caspase-6 is associated with early Alzheimer and Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels correlate with lower cognitive performance in aged humans. Caspase-6 induces axonal degeneration in human primary neuron cultures and causes inflammation and neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To assess whether Caspase-6 causes damage to another neuronal system, a transgenic knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the striatum, the area affected in Huntington disease, and 2...
January 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352174/mechanical-phenotyping-of-k562-cells-by-the-micropipette-aspiration-technique-allows-identifying-mechanical-changes-induced-by-drugs
#13
Alessandro Di Cerbo, Valentina Rubino, Francesca Morelli, Giuseppina Ruggiero, Rosaria Landi, Gianandrea Guidetti, Sergio Canello, Giuseppe Terrazzano, Andrea Alessandrini
Mechanical properties of living cells can be used as reliable markers of their state, such as the presence of a pathological state or their differentiation phase. The mechanical behavior of cells depends on the organization of their cytoskeletal network and the main contribution typically comes from the actomyosin contractile system, in both suspended and adherent cells. In the present study, we investigated the effect of a pharmaceutical formulation (OTC - Ossitetraciclina liquida 20%) used as antibiotic, on the mechanical properties of K562 cells by using the Micropipette Aspiration Technique (MAT)...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352079/identification-and-validation-of-a-new-source-of-low-grain-cadmium-accumulation-in-durum-wheat
#14
Atena Oladzad Abbasabadi, Ajay Kumar, Seyed Pirseyedi, Evan Salsman, Marina Dobrydina, Roshan Sharma Poudel, Wesam A AbuHammad, Shiaoman Chao, Justin D Faris, Elias M Elias
Cadmium (Cd) is a heavy metal that has no known biological function and is toxic for many living organisms. The maximum level of Cd concentration allowed in the international market for wheat grain is 0.2 mg kg-1. Because phenotyping for Cd uptake is expensive and time consuming, molecular markers associated with genes conferring low Cd uptake would expedite selection and lead to the development of durum cultivars with reduced Cd concentrations. Here, we identified single nucleotide polymorphisms (SNPs) associated with a novel low Cd uptake locus in the durum experimental line D041735, which has hexaploid common wheat in its pedigree...
January 19, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29352068/maternal-fetal-disposition-and-metabolism-of-retrorsine-in-pregnant-rats
#15
Xia Li, Xiaojing Yang, E Xiang, Jinyuan Luo, Shuaikai Qiu, Yan Fang, Li Zhang, Yu Guo, Jiang Zheng, Hui Wang
Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants and are commonly present in herbs and foodstuffs, which exhibit hepatotoxicity requiring metabolic activation by cytochrome P450 (CYP) 3A to form the electrophilic metabolites-pyrrolic ester. PAs also cause embryo toxicity, but the metabolic profiles of PAs in fetus and placenta have been far from clear. In this study, we determined the basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta and fetal liver in vitro, and examined the fetal toxicity and bioactivation of RTS in vivo...
January 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29351987/cd83-is-a-new-potential-biomarker-and-therapeutic-target-for-hodgkin-lymphoma
#16
Ziduo Li, Xinsheng Ju, Kenneth Lee, Candice Clarke, Jennifer L Hsu, Edward Abadir, Christian E Bryant, Suzanne Pears, Neroli Sunderland, Scott Heffernan, Annemarie Hennessy, Tsun-Ho Lo, Geoffrey A Pietersz, Fiona Kupresanin, Phillip D Fromm, Pablo A Silveira, Con Tsonis, Wendy A Cooper, Ilona Cunningham, Christina Brown, Georgina J Clark, Derek N J Hart
Chemotherapy and hematopoietic stem cell transplantation are effective treatments for most Hodgkin lymphoma patients, however there remains a need for better tumor-specific target therapy in Hodgkin lymphoma patients with refractory or relapsed disease. We demonstrate that membrane CD83 is a diagnostic and therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to surrounding T cells and interestingly, the trogocytosing CD83+T cells expressed significantly more PD-1 compared to CD83- T cells...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351986/phase-ii-study-of-oral-jak1-jak2-inhibitor-ruxolitinib-in-advanced-relapsed-refractory-hodgkin-lymphoma
#17
Eric Van den Neste, Marc André, Thomas Gastinne, Aspasia Stamatoullas, Corinne Haioun, Amine Belhabri, Oumedaly Reman, Olivier Casasnovas, Hervé Guesquieres, Gregor Verhoef, Marie-José Claessen, Hélène A Poirel, Marie-Christine Copin, Romain Dubois, Peter Vandenberghe, Ioanna-Andrea Stoian, Anne S Cottereau, Sarah Bailly, Laurent Knoops, Franck Morschhauser
JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27...
January 19, 2018: Haematologica
https://www.readbyqxmd.com/read/29351906/edc-impact-molecular-effects-of-developmental-fm-550-exposure-in-wistar-rat-placenta-and-fetal-forebrain
#18
Kylie R Baldwin, Brian Horman, Allison L Phillips, Susan L McRitchie, Scott Watson, Jocelin Deese-Spruill, Dereje Jima, Susan Sumner, Heather Stapleton, Heather Patisaul
Firemaster 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear...
January 19, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29351889/disentangling-the-effects-of-low-ph-and-metal-mixture-toxicity-on-macroinvertebrate-diversity
#19
Riccardo Fornaroli, Alessio Ippolito, Mari J Tolkkinen, Heikki Mykrä, Timo Muotka, Laurie S Balistrieri, Travis S Schmidt
One of the primary goals of biological assessment of streams is to identify which of a suite of chemical stressors is limiting their ecological potential. Elevated metal concentrations in streams are often associated with low pH, yet the effects of these two potentially limiting factors of freshwater biodiversity are rarely considered to interact beyond the effects of pH on metal speciation. Using a dataset from two continents, a biogeochemical model of the toxicity of metal mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative importance of both pH and metals as limiting factors for macroinvertebrate communities...
January 16, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29351884/crucial-role-of-chelatable-iron-in-silver-nanoparticles-induced-dna-damage-and-cytotoxicity
#20
Agnieszka Grzelak, Maria Wojewódzka, Sylwia Meczynska-Wielgosz, Mariusz Zuberek, Dominika Wojciechowska, Marcin Kruszewski
Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O2•-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H2O2 instead of O2•-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity...
January 9, 2018: Redox Biology
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