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https://www.readbyqxmd.com/read/28528302/nanomolar-anti-sickling-compounds-identified-by-ligand-based-pharmacophore-approach
#1
Odailson Santos Paz, Milena de Jesus Pinheiro, Renan Fernandes do Espirito Santo, Cristiane Flora Villarreal, Marcelo Santos Castilho
Adenosine receptors are considered as potential targets for drug development against several diseases. The discovery of subtype 2B adenosine receptors role in erythrocyte sickling process proved its importance to neglected diseases such as sickle cell anemia, which affects approximately 29.000 people around the world, but whose treatment is restricted to just one FDA approved drug (hydroxyurea). In order to widen the therapeutic arsenal available to treat sickle cell anemia patients, it is imperative to identify new lead compounds that modify the sickling course and not just its symptoms...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28526606/identification-of-emsox2-a-member-of-the-sox-family-of-transcription-factors-as-a-potential-regulator-of-echinococcus-multilocularis-germinative-cells
#2
Zhe Cheng, Fan Liu, Mengya Dai, Jianjian Wu, Xiu Li, Xinrui Guo, Huimin Tian, Zhijie Heng, Ying Lu, Xiaoli Chai, Yanhai Wang
Larvae of the tapeworm Echinococcus multilocularis cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The germinative cells, a population of stem cell-like cells, are considered to drive the continuous growth of the metacestodes within the host. The mechanisms and relative molecules controlling the behavior of germinative cells are poorly understood. Sox transcription factors play important roles in maintenance and regulation of stem/progenitor cells. We here describe the identification of a Sox family member in E...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28515501/ismp-medication-error-report-analysis-potential-issues-with-new-basal-insulin-glp-1-fixed-combinations-hydroxyzine-hydroxyurea-mix-up-concomitant-use-of-entresto-and-ace-inhibitors-can-lead-to-serious-outcomes-more-outpatient-oral-cancer-drugs-should-be-in
#3
Michael R Cohen, Judy L Smetzer
These medication errors have occurred in health care facilities at least once. They will happen again-perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program...
April 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/28508322/use-patterns-of-first-line-inhibitors-of-tyrosine-kinase-and-time-to-change-to-second-line-therapy-in-chronic-myeloid-leukemia
#4
Jorge Enrique Machado-Alba, Manuel Enrique Machado-Duque
Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified...
May 15, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28506294/hssb1-associates-with-and-promotes-stability-of-the-blm-helicase
#5
Laura V Croft, Nicholas W Ashton, Nicolas Paquet, Emma Bolderson, Kenneth J O'Byrne, Derek J Richard
BACKGROUND: Maintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions. The BLM helicase is central to the repair of both collapsed DNA replication forks and double strand DNA breaks by homologous recombination. RESULTS: In this study, we demonstrate that hSSB1 and BLM helicase form a complex in cells and the interaction is altered in response to ionising radiation (IR)...
May 15, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28503326/incomplete-paraplegia-caused-by-extramedullary-hematopoiesis-in-a-patient-with-thalassemia-intermedia
#6
Nurhasyimah Hisamud-Din, Nadia Mohd Mustafah, Aishah Ahmad Fauzi, Natiara Mohamad Hashim
INTRODUCTION: Extramedullary hematopoiesis (EMH) is the production of blood cell precursors outside the bone marrow that occur in various hematological diseases. In patients with thalassemia intermedia, ineffective erythropoiesis drives compensatory EMH in the liver, pancreas, pleura, spleen, ribs and spine. CASE PRESENTATION: We describe a patient with thalassemia intermedia who presented with acute neurological symptoms caused by paraspinal EMH, which responded well to combination therapy of steroid, hypertransfusion, laminectomy and excision of pseudotumor and hydroxyurea therapy to boost the formation of fetal haemoglobin...
2017: Spinal Cord Series and Cases
https://www.readbyqxmd.com/read/28500860/interventions-for-preventing-silent-cerebral-infarcts-in-people-with-sickle-cell-disease
#7
REVIEW
Lise J Estcourt, Patricia M Fortin, Sally Hopewell, Marialena Trivella, Carolyn Doree, Miguel R Abboud
BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient...
May 13, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28500682/red-blood-cell-transfusions-during-sickle-cell-anemia-vaso-occlusive-crises-a-report-from-the-magnesium-in-crisis-magic-study
#8
Monica L Hulbert, Julie A Panepinto, J Paul Scott, Robert I Liem, Lawrence J Cook, Timothy Simmons, David C Brousseau
BACKGROUND: Little is known about red blood cell (RBC) transfusion practices for children hospitalized for a sickle cell vaso-occlusive pain crisis (VOC). We hypothesized that transfusion would be associated with the development of acute chest syndrome (ACS), lower hemoglobin (Hb) concentration, and lack of hydroxyurea therapy. STUDY DESIGN AND METHODS: This is a secondary analysis of all children admitted for a sickle cell pain crisis enrolled in the Magnesium in Crisis (MAGiC) randomized trial; all had HbSS or S-β(0) thalassemia...
May 12, 2017: Transfusion
https://www.readbyqxmd.com/read/28500485/hydroxyurea-lactose-interaction-study-in-silico-and-in-vitro-evaluation
#9
Kunal B Bachchhao, R R Patil, C R Patil, Dipak D Patil
The Maillard reaction between hydroxyurea (a primary amine-containing drug) and lactose (used as an excipient) was explored. The adduct of these compounds was synthesized by heating hydroxyurea with lactose monohydrate at 60 °C in borate buffer (pH 9.2) for 12 h. Synthesis of the adduct was confirmed using UV-visible spectroscopy and Fourier transform infrared, differential scanning calorimetry, high-pressure liquid chromatography, and liquid chromatography-mass spectrometry studies. An in silico investigation of how the adduct formation affected the interactions of hydroxyurea with its biological target oxyhemoglobin, to which it binds to generate nitric oxide and regulates fetal hemoglobin synthesis, was carried out...
May 12, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28500170/jak2-inhibitors-for-myeloproliferative-neoplasms-what-is-next
#10
Prithviraj Bose, Srdan Verstovsek
Since its approval in 2011, the Janus kinase (JAK) 1/2 inhibitor ruxolitinib has evolved to become the centerpiece of therapy for myelofibrosis (MF), and its use in patients with hydroxyurea resistant/intolerant polycythemia vera (PV) is steadily increasing. A number of other JAK2 inhibitors have entered clinical testing, but none has been approved yet, and many discontinued. Importantly, the activity of these agents is not restricted to patients with JAK2 V617F or exon 12 mutations. Although JAK2 inhibitors provide substantial clinical benefit, their disease-modifying activity is limited, and rational combinations with other targeted agents are needed, particularly in MF, where survival is short...
May 12, 2017: Blood
https://www.readbyqxmd.com/read/28497125/mapping-ubiquitination-sites-of-s-cerevisiae-mcm10
#11
Tianji Zhang, Brandy L Fultz, Sapna Das-Bradoo, Anja-Katrin Bielinsky
Minichromosome maintenance protein (Mcm) 10 is a part of the eukaryotic replication machinery and highly conserved throughout evolution. As a multivalent DNA scaffold, Mcm10 coordinates the action of proteins that are indispensable for lagging strand synthesis, such as the replication clamp, proliferating cell nuclear antigen (PCNA). The binding between Mcm10 and PCNA serves an essential function during DNA elongation and is mediated by the ubiquitination of Mcm10. Here we map lysine 372 as the primary attachment site for ubiquitin on S...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28495531/the-forkhead-like-transcription-factor-fhl1p-maintains-yeast-replicative-lifespan-by-regulating-ribonucleotide-reductase-1-rnr1-gene-transcription
#12
Akiko Tai, Yuka Kamei, Yukio Mukai
In eukaryotes, numerous genetic factors contribute to the lifespan including metabolic enzymes, signal transducers, and transcription factors. As previously reported, the forkhead-like transcription factor (FHL1) gene was required for yeast replicative lifespan and cell proliferation. To determine how Fhl1p regulates the lifespan, we performed a DNA microarray analysis of a heterozygous diploid strain deleted for FHL1. We discovered numerous Fhl1p-target genes, which were then screened for lifespan-regulating activity...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28486096/key-pharmacogenomic-considerations-for-sickle-cell-disease-patients
#13
Alexandra Kolliopoulou, Apostolos Stratopoulos, Stavroula Siamoglou, Argyro Sgourou, Adamantia Papachatzopoulou, Theodora Katsila, George P Patrinos
Sickle cell disease (SCD), although a monogenic disease, exhibits a complex clinical phenotype that hampers optimum patient stratification and disease management, especially on hydroxyurea treatment. Moreover, theranostics, the combination of diagnostics to individualize and optimize therapeutic interventions, has not been firmly on the forefront of SCD research and clinical management to date. We suggest that if tailor-made theranostics in SCD is envisaged, pharmacogenomics is anticipated to be the way forward...
May 9, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28484512/developing-new-pharmacotherapeutic-approaches-to-treating-sickle-cell-disease
#14
Marilyn J Telen
Survival for patients with SCD has been prolonged by improvements in supportive care, including vaccinations, antibiotic prophylaxis, and overall medical management, including tra nsfusion. However, there remains only one approved, partially effective drug for sickle cell disease-hydroxyurea (hydroxycarbamide). The world desperately needs better ways of both treating and preventing the recurrent painful vaso-occlusive episodes pathognomonic of sickle cell disease as well as the end-organ damage that still leads inexorably to severely shortened life expectancies throughout the world...
February 2017: ISBT Science Series
https://www.readbyqxmd.com/read/28474342/a-retrospective-analysis-of-the-impact-of-treatments-and-blood-counts-on-survival-and-the-risk-of-vascular-events-during-the-course-of-polycythaemia-vera
#15
Anneli Enblom-Larsson, Francois Girodon, Marie Bak, Ditte Hersby, Valérie Jooste, Hans Hasselbalch, Peter Johansson, Björn Andreasson
Vascular and non-vascular complications are common in patients with polycythaemia vera. This retrospective study of 217 patients with polycythaemia vera aimed to determine whether blood counts with respect to different treatments influenced the complication rate and survival. We found that 78 (36%) patients suffered from at least one complication during follow-up. Older age and elevated lactate dehydrogenase at diagnosis were found to be risk factors for vascular complications. When the vascular complication occurred, 41% of the patients with a complication had elevated white blood cells (WBC) compared with 20% of patients without a complication (P = 0·042)...
May 5, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28472781/comparison-of-the-efficacy-among-multiple-chemotherapeutic-interventions-combined-with-radiation-therapy-for-patients-with-cervix-cancer-after-surgery-a-network-meta-analysis
#16
Lei Chang, Ruixia Guo
BACKGROUND: Cervix cancer was the second most common cancer in female. However, there was no network meta-analysis (NMA) comparing the efficacy of the multiple chemotherapeutic interventions combined with radiation therapy in patients after operation. METHODS: Randomized controlled trials were retrieved from PubMed, Embase and Cochrane Library. Overall survival (OS), recurrence-free survival (RFS), incidence of recurrence and distant metastasis were the main outcomes, particularly 5-year OS and PFS were considered as primary outcomes...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28456851/ruxolitinib-reduces-jak2-p-v617f-allele-burden-in-patients-with-polycythemia-vera-enrolled-in-the-response-study
#17
Alessandro Maria Vannucchi, Srdan Verstovsek, Paola Guglielmelli, Martin Griesshammer, Timothy C Burn, Ahmad Naim, Dilan Paranagama, Mahtab Marker, Brian Gadbaw, Jean-Jacques Kiladjian
In patients with polycythemia vera (PV), an elevated JAK2 p.V617F allele burden is associated with indicators of more severe disease (e.g., leukocytosis, splenomegaly, and increased thrombosis risk); however, correlations between allele burden reductions and clinical benefit in patients with PV have not been extensively evaluated in a randomized trial. This exploratory analysis from the multicenter, open-label, phase 3 Randomized Study of Efficacy and Safety in Polycythemia Vera With JAK Inhibitor INCB018424 Versus Best Supportive Care trial evaluated the long-term effect of ruxolitinib treatment on JAK2 p...
April 30, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28447889/bone-marrow-as-a-hematopoietic-stem-cell-source-for-gene-therapy-in-sickle-cell-disease-evidence-from-rhesus-and-scd-patients
#18
Naoya Uchida, Atsushi Fujita, Matthew M Hsieh, Aylin C Bonifacino, Allen E Krouse, Mark E Metzger, Robert E Donahue, John F Tisdale
Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC) source for gene therapy in sickle cell disease (SCD) due to the recognized risk of vaso-occlusive crisis during granulocyte colony-stimulating factor mobilization. We previously established clinically relevant HSC gene transfer in the rhesus model following transplantation of mobilized peripheral blood (PB) CD34(+) cells transduced with lentiviral vectors. In this study, we examined steady state bone marrow (BM) in the rhesus competitive repopulation model and demonstrate similar gene marking in vitro and in vivo, as compared with mobilized PB CD34(+) cells...
April 17, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28447620/dna-replication-licensing-factor-cdc6-and-plk4-kinase-antagonistically-regulate-centrosome-duplication-via-sas-6
#19
Xiaowei Xu, Shijiao Huang, Boyan Zhang, Fan Huang, Wangfei Chi, Jingyan Fu, Gang Wang, Si Li, Qing Jiang, Chuanmao Zhang
Centrosome number is tightly controlled during the cell cycle to ensure proper spindle assembly and cell division. However, the underlying mechanism that controls centrosome number remains largely unclear. We show herein that the DNA replication licensing factor Cdc6 is recruited to the proximal side of the centrioles via cyclin A to negatively regulate centrosome duplication by binding and inhibiting the cartwheel protein Sas-6 from forming a stable complex with another centriole duplication core protein, STIL...
April 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28446303/-prognosis-and-survival-analysis-of-patients-with-essential-thrombocythemia
#20
Mo Chen, Li-Jun Hou, Zeng-Xiang Liu, Hong-Bing Liu, Qiao-Dan Liu
OBJECTIVE: To investigate the survival status and prognosis of patients with essential thrombocythemia(ET) and analyze the prognostic factors for the patients' survival, so as to provide a evidence for clinical treatment and prognosis evaluation. METHODS: A retrospective analysis of 118 patients with ET was conducted in the Fifth Affiliated Hospital of Sun Yat-Sen University and Zhongshan Municipale People's Hospital from December 2002 to December 2013. The clinical characteristics were summarized, such as the survival curve and multi-factor analysis, therefore looking for the disease characteristics and risk factors affecting the survival and prognosis...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
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