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https://www.readbyqxmd.com/read/28636788/role-of-positively-charged-residues-on-the-polar-and-non-polar-faces-of-amphipathic-%C3%AE-helical-antimicrobial-peptides-amps-on-specificity-and-selectivity-for-gram-negative-pathogens
#1
Ziqing Jiang, Colin T Mant, Michael Vasil, Robert S Hodges
We have designed de novo and synthesized eight 26-residue all D-conformation amphipathic α-helical cationic antimicrobial peptides (AMPs), four with "specificity determinants" which provide specificity for prokaryotic cells over eukaryotic cells and four AMPs without specificity determinants. The eight AMPs contain six positively charged Lys residues on the polar face in four different arrangements to understand the role of these residues have on antimicrobial activity against 14 Acinetobacter baumannii strains, 7 of which were resistant to polymyxin B and colistin; 6 diverse Pseudomonas aeruginosa strains and 17 Staphylococcus aureus strains, 9 of which were Methicillin-sensitive (MSSA) and 8 of which were Methicillin-resistant (MRSA)...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28633708/once-daily-dosing-of-amikacin-for-treatment-of-mycobacterium-abscessus-lung-disease
#2
H Lee, Y M Sohn, J Y Ko, S-Y Lee, B W Jhun, H Y Park, K Jeon, D H Kim, S-Y Kim, J E Choi, I J Moon, S J Shin, H J Park, W-J Koh
SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 μg/ml was achieved in 31...
July 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28632322/reduced-intensity-conditioning-allogeneic-transplantation-after-salvage-treatment-with-dt-pace-in-myeloma-patients-relapsing-early-after-autologous-transplant
#3
K Randall, M Kaparou, E Xenou, S Paneesha, B Kishore, A Kanellopoulos, R Lovell, K Holder, J Suhr, L Baker, L Ryan, E Nikolousis
OBJECTIVE: In this retrospective single center study we have looked into the transplant outcomes(overall survival OS, progression free survival PFS,GvHD) and the role of chimerism, DLI and pre-transplant characteristics in patients who had a suboptimal response (<12 months)to an autologous stem cell transplant for myeloma and underwent an Alemtuzumab T-cell depleted reduced intensity allograft(RIC). METHODS: 24 patients were salvaged with 2 cycles of DT-PACE and received a RIC transplant with Fludarabine, Melphalan and Alemtuzumab...
June 20, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28629933/lignans-from-the-root-of-wikstroemia-indica-and-their-cytotoxic-activity-against-panc-1-human-pancreatic-cancer-cells
#4
Hang Chang, Yuwei Wang, Xue Gao, Zehai Song, Suresh Awale, Na Han, Zhihui Liu, Jun Yin
Six new compounds, wikstronin A (1), wikstronin B (2), wikstresinol (3), acetylwikstresinol (4), bis-5',5'-(+)-matairesinol (5), bis-5,5'-(+)-matairesinol (6), together with 20 known compounds (7-26) were isolated from the CH2Cl2 extract of roots of Wikstroemia indica. Structures of compounds 1-6 were determined by extensive NMR and CD spectroscopic analysis. In vitro preferential cytotoxicity of all the isolates was evaluated against a PANC-1 human pancreatic cell line. Compounds 8 and 12 displayed mild preferential cytotoxicity in the nutrient-deprived medium (NDM) and without causing toxicity in normal nutrient-rich conditions...
June 16, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28626600/distant-brain-recurrence-in-patients-with-five-or-more-newly-diagnosed-brain-metastases-treated-with-focal-stereotactic-radiotherapy-alone
#5
Olivia Claire Barrett, Andrew M McDonald, Jonathan W Thompson, Markus Bredel, Gerald McGwin, Kristen O Riley, John B Fiveash
BACKGROUND: To assess the clinical outcomes in patients with greater than 4 newly diagnosed brain metastases treated with focal stereotactic radiotherapy alone. METHODS: All patients with five or more brain metastases who received focal radiotherapy without whole brain radiation or resection were included in this retrospective analysis. Distant brain failure (DBF), overall survival (OS) and toxicity were reported. RESULTS: Thirty-six patients met inclusion with median clinical follow-up of 6...
2017: Journal of Radiosurgery and SBRT
https://www.readbyqxmd.com/read/28624937/acute-toxicity-of-chemical-pesticides-and-plant-derived-essential-oil-on-the-behavior-and-development-of-earthworms-eudrilus-eugeniae-kinberg-and-eisenia-fetida-savigny
#6
Prabhakaran Vasantha-Srinivasan, Sengottayan Senthil-Nathan, Athirstam Ponsankar, Annamalai Thanigaivel, Muthiah Chellappandian, Edward-Sam Edwin, Selvaraj Selin-Rani, Kandaswamy Kalaivani, Wayne B Hunter, Veeramuthu Duraipandiyan, Naif Abdullah Al-Dhabi
Comparative toxicity of two chemical pesticides (temephos and monocrotophos) versus a plant-derived betel leaf oil Piper betle (L.) to earthworm Eudrilus eugeniae (Kinberg) and redworm Eisenia fetida Savigny, historically: Eisenia foetida (Savigny 1826), was evaluated. Mortality rate was more prominent in temephos at 100 μg concentration to both the earthworms in filter paper test (FPT) as well as 10 mg concentration in artificial soil test (AST). In contrast, P. betle does not display much mortality rate to both the earthworms even at 1000 mg of treatment concentrations...
June 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28622920/post-9-11-sarcoidosis-in-wtc-exposed-firefighters-and-emergency-medical-service-workers
#7
Mayris P Webber, Jennifer Yip, Rachel Zeig-Owens, William Moir, Patompong Ungprasert, Cynthia S Crowson, Charles B Hall, Nadia Jaber, Michael D Weiden, Eric L Matteson, David J Prezant
INTRODUCTION: The World Trade Center (WTC) disaster released a huge quantity and variety of toxicants into the environment. To-date, studies from each of the three major cohorts of WTC-exposed workers have suggested "greater than expected" numbers of post-9/11 cases in some workers. We undertook this study to estimate the incidence of post-9/11 sarcoidosis in ∼13,000 male firefighters and EMS workers enrolled in The Fire Department of the City of New York (FDNY) WTC Health Program; to compare FDNY incidence to rates from unexposed, demographically similar men in the Rochester Epidemiology Project (REP); and, to examine rates by level of WTC exposure...
June 7, 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28622691/prospective-randomized-phase-ii-study-of-folfiri-versus-folfox7-in-advanced-gastric-adenocarcinoma-a-chinese-western-cooperative-gastrointestinal-oncology-group-study
#8
Qiu Li, Feng Wen, Chengya Zhou, Meng Qiu, Jiyan Liu, Jing Chen, Cheng Yi, Zhiping Li, Deyun Luo, Feng Xu, Xiaohong Cai, Feng Bi
Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621212/methamphetamine-causes-neurotoxicity-by-promoting-polarization-of-macrophages-and-inflammatory-response
#9
X Li, F Wu, L Xue, B Wang, J Li, Y Chen, T Chen
Macrophages, especially their activation state, are closely related to the progression of neurotoxicity. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (Meth) abuse may lead to long-lasting abnormalities in the neuronal system. The present study investigated the effect of Meth at subtoxic concentration on macrophage activation state and its underlying toxicity to neuronal cells...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28619387/evaluation-of-ameliorative-ability-of-silibinin-against-zidovudine-and-isoniazid-induced-hepatotoxicity-and-hyperlipidaemia-in-rats-role-of-silibinin-in-phase-i-and-ii-drug-metabolism
#10
Raghu Ramanathan, Karthikeyan Sivanesan
HIV/AIDS patients have suppressed immune system, making them vulnerable to many opportunistic infections including tuberculosis (TB). The patients who are co-infected with TB undergo combined regimens with anti-retroviral drugs such as zidovudine (AZT) and anti-tubercular drug such as isoniazid (INH) for therapy leading to hepatotoxicty. Silibinin (SBN), extracted from Silybum marianum commonly called as "Milk thistle" is used against several drugs-induced hepatotoxicity. The present study evaluates the ameliorative effect of SBN against AZT alone, INH alone, and INH + AZT-induced toxic insults to liver of rats...
June 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28618307/meta-analysis-of-selected-toxicity-endpoints-of-cdk4-6-inhibitors-palbociclib-and-ribociclib
#11
REVIEW
R Costa, R B Costa, Sarah M Talamantes, Irene Helenowski, Jonna Peterson, Jason Kaplan, B A Carneiro, Francis J Giles, W J Gradishar
PURPOSE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors such as palbociclib and ribociclib are associated with distinct adverse effects (AEs) compared to other targeted therapies. This meta-analysis of clinical trials summarizes these agents' toxicity profile. METHODS: A librarian-guided literature search was conducted in March of 2017. The trials needed to have at least one of the study arms consisting of palbociclib or ribociclib monotherapy at currently FDA approved dose regimens...
June 12, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28615927/p-tsa-promoted-syntheses-of-5h-benzo-h-thiazolo-2-3-b-quinazoline-and-indeno-1-2-d-thiazolo-3-2-a-pyrimidine-analogs-molecular-modeling-and-in-vitro-antitumor-activity-against-hepatocellular-carcinoma
#12
Amit K Keshari, Ashok K Singh, Vinit Raj, Amit Rai, Prakruti Trivedi, Balaram Ghosh, Umesh Kumar, Atul Rawat, Dinesh Kumar, Sudipta Saha
In our efforts to address the rising incidence of hepatocellular carcinoma (HCC), we have made a commitment to the synthesis of novel molecules to combat Hep-G2 cells. A facile and highly efficient one-pot, multicomponent reaction has been successfully devised utilizing a p-toluenesulfonic acid (p-TSA)-catalyzed domino Knoevenagel/Michael/intramolecular cyclization approach for the synthesis of novel 5H-benzo[h]thiazolo[2,3-b]quinazoline and indeno[1,2-d] thiazolo[3,2-a]pyrimidine analogs bearing a bridgehead nitrogen atom...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28614908/adenoviral-production-of-interleukin-2-at-the-tumor-site-removes-the-need-for-systemic-postconditioning-in-adoptive-cell-therapy
#13
Joao Manuel Santos, Riikka Havunen, Mikko Siurala, Víctor Cervera-Carrascon, Siri Tähtinen, Suvi Sorsa, Marjukka Anttila, Pauliina Karell, Anna Kanerva, Akseli Hemminki
Systemic high-dose interleukin-2 (IL-2) postconditioning has long been utilized in boosting the efficacy of T cells in adoptive cell therapy (ACT) of solid tumors. The resulting severe off-target toxicity of these regimens renders local production at the tumor an attractive concept with possible safety gains. We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28614905/long-term-follow-up-of-chemoimmunotherapy-with-rituximab-oxaliplatin-cytosine-arabinoside-dexamethasone-road-in-patients-with-relapsed-cd20-b-cell-non-hodgkin-lymphoma-results-of-a-study-of-the-mayo-clinic-cancer-research-consortium-mccrc-mc0485-now-known-as
#14
Thomas E Witzig, Patrick B Johnston, Betsy R LaPlant, Paul J Kurtin, Levi D Pederson, Dennis F Moore, Nassim H Nabbout, Daniel A Nikcevich, Kendrith M Rowland, Axel Grothey
Patients with relapsed aggressive non-Hodgkin lymphoma (NHL) are often treated with platinum-based chemoimmunotherapy regimens in preparation for autologous stem cell transplant. We sought to reduce toxicity and maintain efficacy by using oxaliplatin with rituximab, cytarabine and dexamethasone (ROAD) in a phase II clinical trial in patients who had relapsed after one prior regimen. ROAD was delivered q21 days and consisted of rituximab 375 mg/m2 IV weekly x 4 doses (cycle 1 only); dexamethasone 40 mg PO/IV d2 - 5; oxaliplatin 130 mg/m2 IV d2; cytarabine 2000 mg/m2 IV x two doses on days 2 - 3; and pegfilgrastim 6 mg SC on d4...
June 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28612140/a-phase-ii-study-of-ipilimumab-plus-temozolomide-in-patients-with-metastatic-melanoma
#15
Sapna P Patel, Dae Won Kim, Roland L Bassett, Suzanne Cain, Edwina Washington, Wen-Jen Hwu, Kevin B Kim, Nicholas E Papadopoulos, Jade Homsi, Patrick Hwu, Agop Y Bedikian
Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. This potential immunomodulatory effect of temozolomide provides rationale for combination with ipilimumab...
June 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#16
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28610743/valproate-and-sodium-butyrate-attenuate-manganese-decreased-locomotor-activity-and-astrocytic-glutamate-transporters-expression-in-mice
#17
James Johnson, Edward Alain B Pajarillo, Equar Taka, Romonia Reams, Deok-Soo Son, Michael Aschner, Eunsook Lee
Manganese (Mn) is an essential trace element, but chronic overexposure to this metal, either environmentally or occupationally may cause manganism, a disease analogous to Parkinson's disease. Inhibitors of histone deacetylases, such as valproic acid (VPA) and sodium butyrate (NaB) exert neuroprotective effects in various animal models of neurological disorders. Thus, the present study investigated whether VPA or NaB prevent Mn-induced neurotoxicity by assessing locomotor activities and expression of astrocytic glutamate transporters, glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST), in C57BL/6 mice...
June 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28602250/lsu-rdna-based-rflp-assays-for-the-routine-identification-of-gambierdiscus-species
#18
Yihua Lyu, Mindy L Richlen, Taylor R Sehein, Mireille Chinain, Masao Adachi, Tomohiro Nishimura, Yixiao Xu, Michael L Parsons, Tyler B Smith, Tianling Zheng, Donald M Anderson
The Gambierdiscus genus is a group of benthic dinoflagellates commonly associated with ciguatera fish poisoning (CFP), which is generally found in tropical or sub-tropical regions around the world. Morphologically similar species within the genus can vary in toxicity; however, species identifications are difficult or sometimes impossible using light microscopy. DNA sequencing of ribosomal RNA genes (rDNA) is thus often used to identify and describe Gambierdiscus species and ribotypes, but the expense and time can be prohibitive for routine culture screening and/or large-scale monitoring programs...
June 2017: Harmful Algae
https://www.readbyqxmd.com/read/28601972/tak-228-formerly-mln0128-an-investigational-dual-torc1-2-inhibitor-plus-paclitaxel-with-without-trastuzumab-in-patients-with-advanced-solid-malignancies
#19
Howard A Burris, C D Kurkjian, L Hart, S Pant, P B Murphy, S F Jones, R Neuwirth, C G Patel, F Zohren, J R Infante
PURPOSE: This phase I trial evaluated the safety, pharmacokinetic profile, and antitumor activity of investigational oral TORC1/2 inhibitor TAK-228 plus paclitaxel, with/without trastuzumab, in patients with advanced solid malignancies. METHODS: Sixty-seven patients received TAK-228 6-40 mg via three dosing schedules; once daily for 3 days (QDx3d QW) or 5 days per week (QDx5d QW), and once weekly (QW) plus paclitaxel 80 mg/m(2) (dose-escalation phase, n = 47) and with/without trastuzumab 2 mg/kg (expansion phase, n = 20)...
June 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28601705/abvd-or-beacoppbaseline-along-with-involved-field-radiotherapy-in-early-stage-hodgkin-lymphoma-with-risk-factors-results-of-the-european-organisation-for-research-and-treatment-of-cancer-eortc-groupe-d-%C3%A3-tude-des-lymphomes-de-l-adulte-gela-h9-u-intergroup-randomised
#20
Christophe Fermé, José Thomas, Pauline Brice, Olivier Casasnovas, Andrej Vranovsky, Serge Bologna, Pieternella J Lugtenburg, Réda Bouabdallah, Patrice Carde, Catherine Sebban, Houchingue Eghbali, Gilles Salles, Gustaaf W van Imhoff, Antoine Thyss, Evert M Noordijk, Oumédaly Reman, Marnix L M Lybeert, Maud Janvier, Michele Spina, Bruno Audhuy, John M M Raemaekers, Richard Delarue, Bruno Anglaret, Okke de Weerdt, Zora Marjanovic, Robbert J H A Tersteeg, Daphne de Jong, Josette Brière, Michel Henry-Amar
PURPOSE: For early-stage Hodgkin lymphoma (HL), optimal chemotherapy regimen and the number of cycles to be delivered remain to settle down. The H9-U trial compared three modalities of chemotherapy followed by involved-field radiotherapy (IFRT) in patients with stage I-II HL and risk factors (NCT00005584). PATIENTS AND METHODS: Patients aged 15-70 years with untreated supradiaphragmatic HL with at least one risk factor (age ≥ 50, involvement of 4-5 nodal areas, mediastinum/thoracic ratio ≥ 0...
June 7, 2017: European Journal of Cancer
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