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https://www.readbyqxmd.com/read/28809997/twenty-nail-transverse-melanonychia-induced-by-hydroxyurea-case-report-and-review-of-the-literature
#1
Osamuede Osemwota, John Uhlemann, Adam Rubin
<p>Twenty-nail transverse melanonychia from hydroxyurea is a rare phenomenon, only reported four times previously. Here we describe a 51-year-old female who presented with 20-nail transverse melanonychia 3 months after initiating hydroxyurea therapy. Transverse melanonychia is a benign process but can cause patients significant distress, and thus is an entity with which dermatologists should recognize. We then review the cutaneous manifestations, differential diagnosis, and clinical considerations when evaluating patients with transverse melanonychia from hydroxyurea or other causes...
August 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28807928/role-of-translesion-synthesis-dna-polymerases-in-dna-replication-in-the-presence-of-a-weak-dna-polymerase-%C3%AE-in-saccharomyces-cerevisiae
#2
Likui Zhang, Yanchao Huang, Xinyuan Zhu, Yuxiao Wang, Haoqiang Shi, Min Chen, Kunming Dong, Xiaojian Zhou
Translesion synthesis (TLS) DNA polymerases (pols) are often mutagenic for lesion bypass due to their low fidelity. Here, we isolated a weak yeast DNA pol δ mutant that possessed amino acid substitution V592G by genetic selection. The pol3-V592G cells were sensitive to hydroxyurea (HU), which increases the requirement for dNTPs, and their HU sensitivity was suppressed by L612M substitution. We also demonstrated that V592G substitution suppressed the phosphonoacetic acid (PAA) sensitivity of pol3-L612M cells, suggesting a cycle of mutual suppression in the HU- and PAA-sensitive yeast DNA pol δ mutants as similarly observed in the optA1- and PAA-sensitive T4 DNA pol mutants...
August 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28807656/opportunities-for-model-based-precision-dosing-in-the-treatment-of-sickle-cell-anemia
#3
Min Dong, Tomoyuki Mizuno, Alexander A Vinks
Hydroxyurea is the primary pharmacotherapy to prevent complications of sickle cell anemia (SCA). Accumulated clinical experience across multiple age ranges has suggested that the use of an individualized maximum tolerated dose (MTD) will achieve optimal benefit of hydroxyurea treatment. However, the current empirical and trial-and-error approach for dose escalation often results in a lengthy titration process and is not strictly implemented in many clinics. Opportunities exist for pharmacokinetics model-based precision dosing of hydroxyurea to quickly achieve individual MTD...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28783617/an-age-dependent-response-to-hydroxyurea-in-pediatric-sickle-cell-anemia-patients-with-alpha-thalassemia-trait
#4
Lisa Figueiredo, Kerry Morrone, Catherine Wei, Karen Ireland, Hillel W Cohen, Catherine Driscoll, Deepa Manwani
Hydroxyurea (HU) is a key drug therapy for individuals with sickle cell anemia (SCA), yet its clinical and hematologic responses can be variable. Various studies have reported the role of α-thalassemia as one of the most prevalent heritable traits that may modify HU response. We provide data from 62 pediatric and adolescent patients with SCA, 26 with co-inherited α-thalassemia trait. Our data suggest that altered hematologic and clinical responses to HU therapy are noted in adolescent SCA individuals with co-inherited α-thalassemia trait...
July 31, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28782309/study-of-seminal-fluid-parameters-and-fertility-of-male-sickle-cell-disease-patients-and-potential-impact-of-hydroxyurea-treatment
#5
Lulup Kumar Sahoo, Bipin Kishore Kullu, Siris Patel, Nayan Kumar Patel, Pragyan Rout, Prasanta Purohit, Satyabrata Meher
INTRODUCTION: Male Sickle cell disease (SCD) patients often have moderate to severe hypogonadism resulting in abnormal seminal fluid parameters due to testicular dysfunction. Hydroxyurea (HU), the only drug found to be effective in preventing morbidity and mortality in sickle cell disease patients has been found to further aggravate the testicular dysfunction. MATERIAL AND METHODS: This was a prospective study done at a tertiary care hospital over 26 months between September 2011 to October 2013...
June 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28776729/sirt1-activates-the-expression-of-fetal-hemoglobin-genes
#6
Yan Dai, Tyngwei Chen, Heba Ijaz, Elizabeth H Cho, Martin H Steinberg
High fetal hemoglobin (HbF, α2 γ2 ) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells...
August 4, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28775286/elp3-and-dph3-of-schizosaccharomyces-pombe-mediate-cellular-stress-responses-through-trna-lys-uuu-modifications
#7
Desirée Villahermosa, Oliver Fleck
Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28771906/cdk1-interacting-protein-cip1-is-regulated-by-the-s%C3%A2-phase-checkpoint-in-response-to-genotoxic-stress
#8
Ze Zhang, Ping Ren, Ajay A Vashisht, James A Wohlschlegel, David G Quintana, Fanli Zeng
In eukaryotic cells, a surveillance mechanism, the S phase checkpoint, detects and responds to insults that challenge chromosomal replication, arresting cell cycle progression and triggering appropriate events to prevent genomic instability. In the budding yeast Saccharomyces cerevisiae, Mec1/ATM/ATR, and its downstream kinase, Rad53/Chk2, mediate the response to genotoxic stress. In this study, we place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress...
August 3, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28761331/antiglycation-radical-scavenging-and-semicarbazide-sensitive-amine-oxidase-inhibitory-activities-of-acetohydroxamic-acid-in-vitro
#9
Yuh-Hwa Liu, Yeh-Lin Lu, Der-Zen Liu, Wen-Chi Hou
Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen species production, and the levels of AGEs are highly correlated with cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH) is a bacterial urease inhibitor drug used to treat kidney stones and infections in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the AGEs' fluorescent intensities and N(ε)-(carboxymethyl)lysine formation in bovine serum albumin/galactose models, and both showed better and significant differences (P<0...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28759962/effects-of-hydroxyurea-on-blood-rheology-in-sickle-cell-anemia-a-two-years-follow-up-study
#10
Nathalie Lemonne, Berenike Möckesch, Keyne Charlot, Yohann Garnier, Xavier Waltz, Yann Lamarre, Sophie Antoine-Jonville, Maryse Etienne-Julan, Marie-Dominique Hardy-Dessources, Marc Romana, Philippe Connes
The aim of the present study was to test the effects of hydroxyurea (HU) therapy on clinical, hematological and hemorheological parameters in adult patients with sickle cell anemia (SCA). Hematological and hemorheological parameters were measured in 28 SCA patients before HU therapy (i.e., baseline) and at 6, 12 and 24 months of treatment. RBC deformability was determined by ektacytometry at 30 Pa. RBC aggregation properties were investigated by light-backscatter method. Blood viscosity was measured at 225 s-1 by a cone-plate viscometer...
July 25, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28750923/didox-3-4-dihydroxybenzohydroxamic-acid-suppresses-il-33-induced-cytokine-production-in-primary-mouse-mast-cells
#11
Heather L Caslin, Jamie Josephine Avila McLeod, Andrew J Spence, Amina Abdul Qayum, Elizabeth Motunrayo Kolawole, Marcela T Taruselli, Anuya Paranjape, Howard L Elford, John J Ryan
While IgE is considered the primary mediator of mast cell activation, IL-33 contributes substantially in asthma, allergic rhinitis, and atopic dermatitis. To develop effective treatments for allergic disease, it is important to understand the role of therapeutic agents on IL-33 activation. We examined the effect of Didox (3,4-dihydroxybenzohydroxamic acid), an antioxidant and ribonucleotide reductase (RNR) inhibitor, on IL-33-mediated mast cell activation. Didox suppressed IL-6, IL-13, TNF, and MIP-1α (CCL3) production in bone marrow derived mast cells following IL-33 activation...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28749973/replication-stress-affects-the-fidelity-of-nucleosome-mediated-epigenetic-inheritance
#12
Wenzhu Li, Jia Yi, Pamela Agbu, Zheng Zhou, Richard L Kelley, Scott Kallgren, Songtao Jia, Xiangwei He
The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28744838/effects-of-hydroxyurea-exposure-on-the-rat-cerebellar-neuroepithelium-an-immunohistochemical-and-electron-microscopic-study-along-the-anteroposterior-and-mediolateral-axes
#13
Lucía Rodríguez-Vázquez, Joaquín Martí
We present a histological study of the cell death of cerebellar neuroepithelial neuroblasts following treatment with the cytotoxic agent hydroxyurea (HU) during the embryonic life. Pregnant rats were treated with a single dose of HU (300 mg/kg) at embryonic days 13, 14, or 15 of gestation, and their fetuses were studied from 5 to 35 h after treatment to elucidate the mechanisms of HU-induced fetotoxicity. Quantification of several parameters such as the density of pyknotic, mitotic, and PCNA-immunoreactive cells indicated that HU compromises the survival of the cerebellar neuroepithelium neuroblasts...
July 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28744014/low-burden-tp53-mutations-in-chronic-phase-of-myeloproliferative-neoplasms-association-with-age-hydroxyurea-administration-disease-type-and-jak2-mutational-status
#14
B Kubesova, S Pavlova, J Malcikova, J Kabathova, L Radova, N Tom, B Tichy, K Plevova, B Kantorova, K Fiedorova, M Slavikova, V Bystry, J Kissova, B Gisslinger, H Gisslinger, M Penka, J Mayer, R Kralovics, S Pospisilova, M Doubek
The multistep process of TP53 mutation expansion during myeloproliferative neoplasm (MPN) transformation into acute myeloid leukemia (AML) has been documented retrospectively. It is currently unknown how common TP53 mutations with low variant allele frequency (VAF) are, whether they are linked to hydroxyurea (HU) cytoreduction, and what disease progression risk they carry. Using ultra-deep next-generation sequencing, we examined 254 MPN patients treated with HU, interferon alpha-2a or anagrelide and 85 untreated patients...
July 24, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28743817/bacterial-signaling-nucleotides-inhibit-yeast-cell-growth-by-impacting-mitochondrial-and-other-specifically-eukaryotic-functions
#15
Andy Hesketh, Marta Vergnano, Chris Wan, Stephen G Oliver
We have engineered Saccharomyces cerevisiae to inducibly synthesize the prokaryotic signaling nucleotides cyclic di-GMP (cdiGMP), cdiAMP, and ppGpp in order to characterize the range of effects these nucleotides exert on eukaryotic cell function during bacterial pathogenesis. Synthetic genetic array (SGA) and transcriptome analyses indicated that, while these compounds elicit some common reactions in yeast, there are also complex and distinctive responses to each of the three nucleotides. All three are capable of inhibiting eukaryotic cell growth, with the guanine nucleotides exhibiting stronger effects than cdiAMP...
July 25, 2017: MBio
https://www.readbyqxmd.com/read/28736939/fetal-hemoglobin-in-sickle-cell-anemia-the-arab-indian-haplotype-and-new-therapeutic-agents
#16
REVIEW
Alawi H Habara, Elmutaz M Shaikho, Martin H Steinberg
Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly two-fold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation...
July 24, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28727801/proponent-or-collaborative-physician-perspectives-and-approaches-to-disease-modifying-therapies-in-sickle-cell-disease
#17
Nitya Bakshi, Cynthia B Sinha, Diana Ross, Kirshma Khemani, George Loewenstein, Lakshmanan Krishnamurti
Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider...
2017: PloS One
https://www.readbyqxmd.com/read/28700486/progression-of-primary-myelofibrosis-to-polycythemia-vera-a-case-report
#18
Yan Guo, Wenwei Xu, Lin Dong, Ning Huang, Kehong Bi
RATIONALE: This case report describes the progression of primary myelofibrosis (PMF) to polycythemia vera (PV), and discuss its potential mechanisms. PATIENT CONCERNS: The patient was admitted because of abdominal discomfort and enlarged spleen for 19 months. DIAGNOSIS: A case of PMF progressed to PV was retrospectively analyzed. There were 19 months between the diagnosis of PMF and PV. The JAK2 V617F mutation was positive before and after the diagnosis of PV; however, new chromosomal abnormalities were detected during the progression...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28699191/a-reappraisal-of-the-benefit-risk-profile-of-hydroxyurea-in-polycythemia-vera-a-propensity-matched-study
#19
Tiziano Barbui, Alessandro Maria Vannucchi, Guido Finazzi, Maria Chiara Finazzi, Arianna Masciulli, Alessandra Carobbio, Arianna Ghirardi, Gianni Tognoni
The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To assure comparability, we conducted a propensity score matching analysis...
July 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28696844/comparison-of-micrornas-mediated-in-reactivation-of-the-%C3%AE-globin-in-%C3%AE-thalassemia-patients-responders-and-non-responders-to-hydroxyurea
#20
Mohammad T Hojjati, Azita Azarkeivan, Ali A Pourfathollah, Naser Amirizadeh
Drug induction of Hb F seems to be an ideal therapy for patients with hemoglobin (Hb) disorders, and many efforts have been made to reveal the mechanism behind it. Thus, we examined in vivo expression of some microRNAs (miRNAs) that are thought to be involved in this process. Among β-thalassemia (β-thal) patients who were undergoing hydroxyurea (HU) therapy in the past 3 months and five healthy individuals, five responders and five non-responders, were also included in the study. Erythroid progenitors were isolated by magnetic activated cell sorting (MACS) and miRNA expression analyzed using reverse transcription-polymerase chain reaction (RT-PCR)...
March 2017: Hemoglobin
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