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https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#1
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28107724/effect-of-sole-or-combined-administration-of-nitrate-and-3-nitro-1-propionic-acid-on-fermentation-and-salmonella-survivability-in-alfalfa-fed-rumen-cultures-in-vitro
#2
Alejandro Castañeda Correa, Julian Trachsel, Heather K Allen, Agustin Corral-Luna, Hector Gutierrez-Bañuelos, Pedro Antonia Ochoa-Garcia, Oscar Ruiz-Barrera, Michael E Hume, Todd R Callaway, Roger B Harvey, Ross C Beier, Robin C Anderson, David J Nisbet
Ruminal methanogenesis is a digestive inefficiency resulting in the loss of dietary energy consumed by the host and contributing to environmental methane emission. Nitrate is being investigated as a feed supplement to reduce rumen methane emissions but safety and efficacy concerns persist. To assess potential synergies of co-administering sub-toxic amounts of nitrate and 3-nitro-1-propionate (NPA) on fermentation and Salmonella survivability with an alfalfa-based diet, ruminal microbes were cultured with additions of 8 or 16mM nitrate, 4 or 12mM NPA or their combinations...
January 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28107698/the-natural-flavonoid-apigenin-sensitizes-human-cd44-prostate-cancer-stem-cells-to-cisplatin-therapy
#3
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107667/two-opposite-dose-dependent-effects-of-diazinon-on-the-motor-activity-of-the-rat-ileum
#4
Saša M Trailović, Djordje S Marjanović, Teodora Vidonja Uzelac, Mirjana Milovanović, Jelena Nedeljković Trailović
Acute poisoning with OPs may lead to a range of neurological effects, which cannot be explained by AChE inhibition alone. Several OPs interact directly with cholinergic receptors in mammals, but such data does not exist for invertebrates. The aim of current study was to investigate the direct and indirect effects of diazinon on the contractions of rat ileum and to compare those effects on the nervemuscle preparation of the Ascaris suum. In the presence of increasing concentrations of diazinon (3, 10 and 30nM), EFS-induced ileal contractions were increased significantly...
January 10, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28107620/chemical-interaction-of-protein-cysteine-residues-with-reactive-metabolites-of-methyleugenol
#5
Yukun Feng, Hui Wang, Qian Wang, Wenlin Huang, Ying Peng, Jiang Zheng
Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME...
January 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28107569/use-of-higher-maximum-doses-and-infusion-rates-compared-with-those-used-in-standard-unfractionated-heparin-therapy-is-associated-with-adequate-anticoagulation-without-increased-bleeding-in-both-obese-and-nonobese-patients-with-cardiovascular-indications
#6
Catherine K Floroff, Nicole M Palm, Daniel H Steinberg, Eric R Powers, Barbara S Wiggins
STUDY OBJECTIVE: To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight-based dosing recommendations compared with an aggressive weight-based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non-ST-Segment Elevation Myocardial Infarction or unstable angina (NSTEMI/UA) or atrial fibrillation. DESIGN: Retrospective cohort study...
January 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28107559/a-randomized-double-blind-placebo-controlled-dose-escalation-first-in-man-study-phase-0-to-assess-the-safety-and-efficacy-of-topical-cytosolic-phospholipase-a2-inhibitor-avx001-in-patients-with-mild-to-moderate-plaque-psoriasis
#7
S H Omland, A Habicht, P Damsbo, J Wilms, B Johansen, R Gniadecki
BACKGROUND: Cytosolic Phospholipase A2 (cPLA2α) is an enzyme suggested as a therapeutic target in inflammatory skin diseases. AVX001, a cPLA2α-inhibitor was investigated in a randomized, double-blind, placebo-controlled, split-design, first-in-man study in patients with mild to moderate psoriasis. OBJECTIVES: The primary objective was to evaluate cutaneous safety and tolerability of AVX001 in doses from 0.002%-5.0%. Safety was assessed as local skin reaction adverse events (LSRAE) grade 3-4...
January 20, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28107554/inclusion-of-a-variable-rbe-into-proton-and-photon-plan-comparison-for-various-fractionation-schedules-in-prostate-radiation-therapy
#8
Jakob Ödén, Kjell Eriksson, Iuliana Toma-Dasu
PURPOSE: A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions...
January 20, 2017: Medical Physics
https://www.readbyqxmd.com/read/28107553/protective-effect-of-n-n-dimethylthiourea-against-stress-induced-gastric-mucosal-lesions-in-rats
#9
Yoshiji Ohta, Koji Yashiro, Takashi Kobayashi, Kazuo Inui, Junji Yoshino
In the present study, we examined the protective effect of N,N'-dimethylthiourea (DMTU), a scavenger of hydroxyl radical (•OH), against water-immersion restraint stress (WIRS)-induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase, an index of tissue neutrophil infiltration, pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide, and NOx (nitrite/nitrate), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal non-protein SH and vitamin C and gastric adherent mucus...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28107527/effects-of-the-administration-of-25-oh-vitamin-d3-in-an-experimental-model-of-chronic-kidney-disease-in-animals-null-for-1-alpha-hydroxylase
#10
Noelia Torremadé, Milica Bozic, David Goltzman, Elvira Fernandez, José M Valdivielso
The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals...
2017: PloS One
https://www.readbyqxmd.com/read/28107514/karyopherin-alpha-proteins-regulate-oligodendrocyte-differentiation
#11
Benjamin M Laitman, John N Mariani, Chi Zhang, Setsu Sawai, Gareth R John
Proper regulation of the coordinated transcriptional program that drives oligodendrocyte (OL) differentiation is essential for central nervous system myelin formation and repair. Nuclear import, mediated in part by a group of karyopherin alpha (Kpna) proteins, regulates transcription factor access to the genome. Understanding how canonical nuclear import functions to control genomic access in OL differentiation may aid in the creation of novel therapeutics to stimulate myelination and remyelination. Here, we show that members of the Kpna family regulate OL differentiation, and may play distinct roles downstream of different pro-myelinating stimuli...
2017: PloS One
https://www.readbyqxmd.com/read/28107478/correction-high-dose-opioid-prescribing-and-opioid-related-hospitalization-a-population-based-study
#12
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0167479.].
2017: PloS One
https://www.readbyqxmd.com/read/28107465/lead-exposure-induces-weight-gain-in-adult-rats-accompanied-by-dna-hypermethylation
#13
Honglin Sun, Ningjian Wang, Xiaomin Nie, Li Zhao, Qin Li, Zhen Cang, Chi Chen, Meng Lu, Jing Cheng, Hualing Zhai, Fangzhen Xia, Lin Ye, Yingli Lu
OBJECTIVE: Previous studies have revealed the association of lead (Pb) exposure with obesity. DNA methylation alteration has been suggested to be one of the regulatory mechanisms of obesity. We aimed to explore whether Pb exposure is related with weight gain and DNA methylation alteration. METHODS: Male adult 8 week Wistar rats were divided into 5 groups: the normal chow diet (NCD); the NCD+0.05%Pb; the NCD+0.15%Pb; the NCD+0.45%Pb and the high fat diet. Rats were exposed to different dosages of Pb through drinking water for 21 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28107421/peroxiporin-expression-is-an-important-factor-for-cancer-cell-susceptibility-to-therapeutic-h2o2-implications-for-pharmacological-ascorbate-therapy
#14
Dieanira Erudaitius, Andrew Huang, Sarah Kazmi, Garry R Buettner, Victor G J Rodgers
Cancer cell toxicity to therapeutic H2O2 varies widely depending on cell type. Interestingly, it has been observed that different cancer cell types have varying peroxiporin expression. We hypothesize that variation in peroxiporin expression can alter cell susceptibility to therapeutic H2O2 concentrations. Here, we silence peroxiporin aquaporin-3 (AQP3) on the pancreatic cancer cell line MIA PaCa-2 and compare clonogenic survival response to the wild-type. The results showed a significantly higher surviving fraction in the clonogenic response for siAQP3 MIA PaCa-2 cells at therapeutic H2O2 doses (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28107415/serum-uric-acid-and-progression-of-kidney-disease-a-longitudinal-analysis-and-mini-review
#15
Ching-Wei Tsai, Shih-Yi Lin, Chin-Chi Kuo, Chiu-Ching Huang
BACKGROUND: Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan. METHODS: Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011...
2017: PloS One
https://www.readbyqxmd.com/read/28107357/vasopressor-use-for-severe-hypotension-a-multicentre-prospective-observational-study
#16
Francois Lamontagne, Deborah J Cook, Maureen O Meade, Andrew Seely, Andrew G Day, Emmanuel Charbonney, Karim Serri, Yoanna Skrobik, Paul Hebert, Charles St-Arnaud, Hector Quiroz-Martinez, Michaël Mayette, Daren K Heyland
BACKGROUND: The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines...
2017: PloS One
https://www.readbyqxmd.com/read/28107310/the-renin-inhibitor-aliskiren-protects-rat-lungs-from-the-histopathologic-effects-of-fat-embolism
#17
Amanda N Fletcher, Agostino Molteni, Rakesh Ponnapureddy, Chirag Patel, Mark Pluym, Alan M Poisner
BACKGROUND: Fat embolism (FE) and the consequent FE syndrome occurring after trauma or surgery can lead to serious pulmonary injury, including ARDS and death. Current treatment of FE syndrome is limited to supportive therapy. We have shown in a rat model that the renin angiotensin system plays a significant role in the pathophysiology of FE because drugs interfering with the renin angiotensin system, captopril and losartan reduce the histopathologic pulmonary damage. The purpose of the current study was to determine if inhibition of renin by aliskiren, an FDA-approved drug for treating hypertension, would produce effective protection in the same model...
February 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28107301/implementation-of-a-pediatric-orthopaedic-bundle-to-reduce-surgical-site-infections
#18
Jan Schriefer, James Sanders, Julie Michels, Kori Wolcott, Connor Ruddy, Jenna Hanson
Surgical site infections (SSIs) cost an estimated $27,288 per case. An analysis of the National Surgical Quality Improvement Program data at the University of Rochester Medical Center suggested that rates of SSIs could be lowered in comparison with both peers and baseline. The aim of this study was to reduce the number of SSIs to zero through the implementation of a "bundle" or a combination of practices. Meetings were held with the multidisciplinary care team that includes surgeons and staff from pediatric pharmacy, pediatric infectious diseases, anesthesia, and nursing to create a care bundle for all pediatric orthopaedic surgery patients...
January 2017: Orthopaedic Nursing
https://www.readbyqxmd.com/read/28107279/prevalence-and-risk-factors-for-symptoms-of-methotrexate-intolerance-in-pediatric-inflammatory-bowel-disease
#19
Claire Dupont-Lucas, Charlotte Grandjean-Blanchet, Bertrand Leduc, Martina Tripcovici, Christine Larocque, France Gervais, Prévost Jantchou, Devendra Amre, Colette Deslandres
BACKGROUND: Methotrexate (MTX) intolerance is defined as gastrointestinal and behavioral symptoms occurring before or after MTX administration that may lead to treatment discontinuation. The aim of this study was to determine prevalence of MTX intolerance in pediatric inflammatory bowel disease (IBD) using the Methotrexate Intolerance Severity Score developed in rheumatology and to identify risk factors for MTX intolerance. METHODS: Patients with pediatric IBD followed in the IBD clinic of Sainte Justine Hospital who had received MTX for IBD between 2004 and 2016 and were still actively on MTX were invited to fill out the Methotrexate Intolerance Severity Score questionnaire...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28107255/high-methotrexate-triglutamate-level-is-an-independent-predictor-of-adverse-effects-in-asian-indian-rheumatoid-arthritis-patients-a-preliminary-study
#20
Amit Sandhu, Varun Dhir, Archana Bhatnagar, Veena Dhawan, Jasbinder Kaur, Ankita Sood, Shankar Naidu, Shabeer Ahmad, Neelam Varma, Aman Sharma, Shefali Sharma
BACKGROUND: It is unclear whether erythrocyte methotrexate polyglutamate levels (MTX-glun) are associated with response or adverse effects to methotrexate in rheumatoid arthritis. This preliminary study evaluated their utility in Asian-Indian patients over 24 weeks. METHODS: Rheumatoid arthritis patients were started on oral methotrexate at a dose of 15 mg per week, which was escalated to 25 mg by 12 weeks and continued till 24 weeks. Erythrocyte (RBC) MTX-glu1 to MTX-glu5 levels (nmol/L RBC) were determined at 4, 8, 16, and 24 weeks by using reverse-phase high-performance liquid chromatography...
January 19, 2017: Therapeutic Drug Monitoring
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