Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions.
An abnormal hemoglobin resulting from the substitution of valine for glutamic acid at position 6 of the beta chain of the globin moiety. The heterozygous state results in sickle cell trait, the homozygous in sickle cell anemia.
Oxygen-carrying RED BLOOD CELLS in mammalian blood that are abnormal in structure or function.
A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.
Seven membered heterocyclic rings containing a NITROGEN atom.
A compound formed by the combination of hemoglobin and oxygen. It is a complex in which the oxygen is bound directly to the iron without causing a change from the ferrous to the ferric state.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)

Differences in the actions of some blockers of the calcium-activated potassium permeability in mammalian red cells. (1/147)

1. The actions of some inhibitors of the Ca2+-activated K+ permeability in mammalian red cells have been compared. 2. Block of the permeability was assessed from the reduction in the net loss of K+ that followed the application of the Ca2+ ionophore A23187 (2 microM) to rabbit red cells suspended at a haematocrit of 1% in a low potassium solution ([K]0 0.12-0.17 mM) at 37 degrees C. Net movement of K+ was measured using a K+-sensitive electrode placed in the suspension. 3. The concentrations (microM +/- s.d.) of the compounds tested causing 50% inhibition of K+ loss were: quinine, 37 +/- 3; cetiedil, 26 +/- 1; the cetiedil congeners UCL 1269, UCL 1274 and UCL 1495, approximately 150, 8.2 +/- 0.1, 0.92 +/- 0.03 respectively; clotrimazole, 1.2 +/- 0.1; nitrendipine, 3.6 +/- 0.5 and charybdotoxin, 0.015 +/- 0.002. 4. The characteristics of the block suggested that compounds could be placed in two groups. For one set (quinine, cetiedil, and the UCL congeners), the concentration-inhibition curves were steeper (Hill coefficient, nH, > or = 2.7) than for the other (clotrimazole, nitrendipine, charybdotoxin) for which nH approximately 1. 5. Compounds in the first set alone became less active on raising the concentration of K+ in the external solution to 5.4 mM. 6. The rate of K+ loss induced by A23187 slowed in the presence of high concentrations of cetiedil and its analogues, suggesting a use-dependent component to the inhibitory action. This was not seen with clotrimazole. 7. The blocking action of the cetiedil analogue UCL 1274 could not be overcome by an increase in external Ca2+ and its potency was unaltered when K+ loss was induced by the application of Pb2+ (10 microM) rather than by A23187. 8. These results, taken with the findings of others, suggest that agents that block the red cell Ca2+-activated K+ permeability can be placed in two groups with different mechanisms of action. The differences can be explained by supposing that clotrimazole and charybdotoxin act at the outer face of the channel whereas cetiedil and its congeners may block within it, either at or near the K+ binding site that determines the flow of K+.  (+info)

RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice. (2/147)

Pre-clinical evaluation has demonstrated that 2-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]-2-methylpropi onic acid (RSR13) acts as an allosteric effector of haemoglobin (Hb). RSR13 binding to Hb results in decreased haemoglobin-oxygen (Hb-O2) affinity, improved tumour oxygenation, and enhanced radiation-induced cell killing in several experimental tumour systems. In the present work, ex vivo clonogenic survival analyses are applied in two murine tumour systems to characterize the relationship between the magnitude of decrease in Hb-O2 affinity and radiosensitization, the influence of inspired pO2 upon this effect, and the efficacy of combining RSR13 and radiation during a course of repeated radiation exposures. For FSaII tumours in C3H mice breathing air, 100 mg kg(-1) RSR13 administered intraperitoneally produced an enhancement ratio (ER) of 1.3, but there was marked desensitization at a RSR13 dose of 300 mg kg(-1) (ER 0.6). The most likely reason for the increased radioresistance was insufficient oxygen loading of Hb in the pulmonary circulation due to reduced haemoglobin-oxygen affinity because carbogen breathing combined with 300 mg kg(-1) RSR13 reversed the effect and produced an ER of 1.8. In SCCVII tumours in C3H mice irradiated with eight fractions of 2.5 Gy over 4 days, the surviving fraction was reduced to 58-67% of control values when RSR13 was combined with radiation on days 1 and 2, days 3 and 4, or days 1-4. These results confirm that combining RSR13 and irradiation within a fractionated course of clinically relevant low-dose exposures provides significant radiosensitization. Additional preclinical experimentation is needed to define better the optimum dose-scheduling conditions for clinical applications.  (+info)

Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity. (3/147)

Conventional approaches for the treatment of myocardial ischemia increase coronary blood flow or reduce myocardial demand. To determine whether a rightward shift in the hemoglobin-oxygen saturation curve would reduce the metabolic and contractile effects of a myocardial oxygen-supply imbalance, we studied the impact of a potent synthetic allosteric modifier of hemoglobin-oxygen affinity, a 2-[4-[[(3,5-disubstituted anilino)carbonyl]methyl] phenoxy] -2-methylproprionic acid derivative (RSR13), during low-flow ischemia. Changes in myocardial high-energy phosphate levels and pH were studied by 31P nuclear magnetic resonance (NMR) spectroscopy in 12 open-chest dogs randomized to receive RSR13 or vehicle control during a reversible reduction of left anterior descending (LAD) coronary artery blood flow. Changes in cardiac metabolites and regional ventricular function studied by pressure segment-length relations were also investigated in additional animals before and after RSR13 administration during low-flow LAD ischemia. The intravenous administration of RSR13 before ischemia resulted in a substantial increase in the mean hemoglobin p50 and attenuated the decline in cardiac creatine phosphate/adenosine triphosphate (PCr/ATP), percent PCr, and pH during ischemia without a change in regional myocardial blood flow, heart rate, or systolic blood pressure. RSR13 given after the onset of low-flow ischemia also improved cardiac PCr/ATP ratios and regional function as measured by fractional shortening and regional work. Thus, synthetic allosteric reduction in hemoglobin-oxygen affinity may be a new and important therapeutic strategy to ameliorate the metabolic and functional consequences of cardiac ischemia.  (+info)

Persistent respiratory effects in survivors of the Bhopal disaster. (4/147)

OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the development of persistent obstructive airways disease. DESIGN: Cross sectional survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES: Self reported respiratory symptoms; indices of lung function measured by simple spirometry and adjusted for age, sex, and height according to Indian derived regression equations. RESULTS: Respiratory symptoms were significantly more common and lung function (percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and FEV1/FEV ratio) was reduced among those reporting exposure to the gas leak. The frequency of symptoms fell as exposure decreased (as estimated by distance lived from the plant), and lung function measurements displayed similar trends. These findings were not wholly accounted for by confounding by smoking or literacy, a measure of socioeconomic status. Lung function measurements were consistently lower in those reporting symptoms. CONCLUSION: Our results suggest that persistent small airways obstruction among survivors of the 1984 disaster may be attributed to gas exposure.  (+info)

The reaction of deoxy-sickle cell hemoglobin with hydroxyurea. (5/147)

In addition to its capacity to increase fetal hemoglobin levels, other mechanisms are implicated in hydroxyurea's ability to provide beneficial effects to patients with sickle cell disease. We hypothesize that the reaction of hemoglobin with hydroxyurea may play a role. It is shown that hydroxyurea reacts with deoxy-sickle cell hemoglobin (Hb) to form methemoglobin (metHb) and nitrosyl hemoglobin (HbNO). The products of the reaction as well as the kinetics are followed by absorption spectroscopy and electron paramagnetic resonance (EPR) spectroscopy. Analysis of the kinetics shows that the reaction can be approximated by a pseudo-first order rate constant of 3.7x10(-4) (1/(s.M)) for the disappearance of deoxy-sickle cell hemoglobin. Further analysis shows that HbNO is formed at an observed average rate of 5.25x10(-5) (1/s), three to four times slower than the rate of formation of metHb. EPR spectroscopy is used to show that the formation of HbNO involves the specific transfer of NO from the NHOH group of hydroxyurea. The potential importance of this reaction is discussed in the context of metHb and HbNO being able to increase the delay time for sickle cell hemoglobin polymerization and HbNO's vasodilating capabilities through conversion to S-nitrosohemoglobin.  (+info)

Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study, a phase I/II trial. Pediatric Hydroxyurea Group. (6/147)

Previous studies have determined the short-term toxicity profile, laboratory changes, and clinical efficacy associated with hydroxyurea (HU) therapy in adults with sickle cell anemia. The safety and efficacy of this agent in pediatric patients with sickle cell anemia has not been determined. Children with sickle cell anemia, age 5 to 15 years, were eligible for this multicenter Phase I/II trial. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d unless the patient experienced laboratory toxicity. Patients were monitored by 2-week visits to assess compliance, toxicity, clinical adverse events, growth parameters, and laboratory efficacy associated with HU treatment. Eighty-four children were enrolled between December 1994 and March 1996. Sixty-eight children reached maximum tolerated dose (MTD) and 52 were treated at MTD for 1 year. Significant hematologic changes included increases in hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, and fetal hemoglobin parameters, and decreases in white blood cell, neutrophil, platelet, and reticulocyte counts. Laboratory toxicities typically were mild, transient, and were reversible upon temporary discontinuation of HU. No life-threatening clinical adverse events occurred and no child experienced growth failure. This Phase I/II trial shows that HU therapy is safe for children with sickle cell anemia when treatment was directed by a pediatric hematologist. HU in children induces similar laboratory changes as in adults. Phase III trials to determine if HU can prevent chronic organ damage in children with sickle cell anemia are warranted.  (+info)

Acetylation of human hemoglobin by methyl acetylphosphate. Evidence of broad regio-selectivity revealed by NMR studies. (7/147)

The development of chemical modification agents that reduce the tendency of sickle hemoglobin (HbS) to aggregate represents an important chemotherapeutic goal. Methyl acetylphosphate (MAP) has been reported to bind to the 2,3-diphosphoglycerate (2,3-DPG) binding site of hemoglobin, where it selectively acetylates residues, resulting in increased solubility of HbS. We have prepared [1-(13)C]MAP and evaluated the adduct formation with hemoglobin using (1)H-(13)C HMQC and HSQC NMR studies. These spectra of the acetylated hemoglobin adducts showed 10-11 well resolved adduct peaks, indicating that the acetylation was not highly residue specific. The chemical shift pattern observed is in general similar to that obtained recently using [1'-(13)C]aspirin as the acetylating agent (Xu, A. S. L., Macdonald, J. M., Labotka, R. J., and London, R. E. (1999) Biochim. Biophys. Acta 1432, 333-349). Blocking the 2, 3-DPG binding site with inositol hexaphosphate (IHP) resulted in a selective reduction in intensity of adduct resonances, presumably corresponding to residues located in the 2,3-DPG binding cleft. The pattern of residue protection appeared to be identical to that observed in our previous study using IHP and labeled aspirin. Pre-acetylation of hemoglobin using unlabeled MAP, followed by acetylation with [1'-(13)C]aspirin indicated a general protective effect, with the greatest reduction of intensity for resonances corresponding to acetylated residues in the 2,3-DPG binding site. These studies indicated that both MAP and aspirin exhibit similar, although not identical, acetylation profiles and target primarily the betaLys-82 residue in the 2,3-DPG binding site, as well as sites such as betaLys-59 and alphaLys-90, which are not located in the beta-cleft of hemoglobin.  (+info)

Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. French Study Group on Sickle Cell Disease. (8/147)

AIM: To evaluate the tolerance of hydroxyurea in children affected with sickle cell disease. DESIGN: Questionnaire study of French physicians likely to treat patients with sickle cell disease. Data were collected on 101 children with sickle cell disease, treated for a median of 22 months, 36 of whom were treated for more than three years. 13 children were younger than 5 years of age at inclusion. RESULTS: Hydroxyurea was stopped for medical reasons in 11 patients: 6 failures, 1 pregnancy, 1 cutaneous rash, 1 leg ulcer, 1 lupus. Acute lymphoblastic leukaemia occurred in a girl treated for 1.5 months with hydroxyurea, this short interval arguing against a causative association. One 17 year old boy had paraparesis after 8 years of treatment. CONCLUSIONS: No major short or medium term toxicity was related to hydroxyurea in this cohort of 101 children. However, the number of children treated for more than 3 years is too few to make firm conclusions on the long term tolerance of this drug.  (+info)

Sickle cell anemia is caused by mutations in the HBB gene that codes for hemoglobin. The most common mutation is a point mutation at position 6, which replaces the glutamic acid amino acid with a valine (Glu6Val). This substitution causes the hemoglobin molecule to be unstable and prone to forming sickle-shaped cells.

The hallmark symptom of sickle cell anemia is anemia, which is a low number of healthy red blood cells. People with the condition may also experience fatigue, weakness, jaundice (yellowing of the skin and eyes), infections, and episodes of severe pain. Sickle cell anemia can also increase the risk of stroke, heart disease, and other complications.

Sickle cell anemia is diagnosed through blood tests that measure hemoglobin levels and the presence of sickle cells. Treatment typically involves managing symptoms and preventing complications with medications, blood transfusions, and antibiotics. In some cases, bone marrow transplantation may be recommended.

Prevention of sickle cell anemia primarily involves avoiding the genetic mutations that cause the condition. This can be done through genetic counseling and testing for individuals who have a family history of the condition or are at risk of inheriting it. Prenatal testing is also available for pregnant women who may be carriers of the condition.

Overall, sickle cell anemia is a serious genetic disorder that can significantly impact quality of life and life expectancy if left untreated. However, with proper management and care, individuals with the condition can lead fulfilling lives and manage their symptoms effectively.

... is a vasodilator and an anti-sickling agent. Alavi JB (May 1984). "Sickle cell anemia. Pathophysiology and treatment ...
... an antisickling agent, using a novel surrogate marker". In 1994 he moved into the role of Medical Director at the contract ...
Antineoplastic Agents - Substances that inhibit or prevent the proliferation of neoplasms. Antisickling Agents - Agents used to ... Due to its chemical properties hydroxyurea was explored as an antisickling agent in the treatment of hematological conditions. ... This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering ... Enzyme Inhibitors - Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme ...
... hematologic agents MeSH D27.505.954.502.119 - anticoagulants MeSH D27.505.954.502.135 - antisickling agents MeSH D27.505. ... antiviral agents MeSH D27.505.954.122.388.077 - anti-retroviral agents MeSH D27.505.954.122.388.077.088 - anti-hiv agents MeSH ... tocolytic agents MeSH D27.505.954.016 - anti-allergic agents MeSH D27.505.954.122 - anti-infective agents MeSH D27.505.954.122. ... tranquilizing agents MeSH D27.505.696.277.950.015 - anti-anxiety agents MeSH D27.505.696.277.950.025 - antimanic agents MeSH ...
Antisickling Agents / pharmacology * Antisickling Agents / therapeutic use * Biomarkers * Clinical Decision-Making * Diagnosis ... The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology. ...
Antisickling Agents - Preferred Concept UI. M0001501. Scope note. Agents used to prevent or reverse the pathological events ... Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions.. ... Agents, Antisickling. Agents, Desickling. Desickling Agents. Tree number(s):. D27.505.954.502.135. ...
Ursolic acid found in scent leaves is an Anti-sickling agent.. This compound battles for the creation of unusual, rigorous ...
... microscopy of polarization applied to the quantification of the polymerization due effects of the anti-sickling agents in the ... Quantitative effect of Hydroxyurea as anti-sickling agent in the molecular polymerization of the Sickle Cell Anemia is analyzed ... With this study it is developed a methodology and a technology that can be used in subsequent studies with other anti-sickling ... microscopy of polarization applied to the quantification of the polymerization due effects of the anti-sickling agents in the ...
These results reveal the potential role for both red and white flower extracts as possible antisickling agents in sickle cell ... The antisickling and antioxidant effects of the flowers of P. ellipticum (Kunth) Dugand (red) and P. ellipticum cultivar alba ( ... Comparative antisickling and antioxidant activities of Pseudobombax ellipticum cultivars in relation to their metabolite ... Both red and white flowers exhibited antioxidant and antisickling activities. In DPPH assay, lower IC50 (34.89 ± 0.98 and 53.28 ...
Iyamu EW, Turner EA, Asakura T. In vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Br J ...
... negatively with pretreatment with the antisickling agent Aes-103 (5-hydroxymethyl-2-furfural) (= ?0.766 = 0.002) and positively ... definitely associated with predictable physiologic and medical parameters and is altered from the putative antisickling agent ...
Antisickling Agents. *Butyrates. *Globins. *Hematopoiesis. *beta-Thalassemia. See all (14) concept(s) ...
Molecular docking and its application in search of antisickling agent from Carica papaya. Das, Dibya Ranjan; Kumar, Dhanesh; ...
Antisickling Agents *Blood Substitutes *Bone Density Conservation Agents *Cardiotonic Agents *Central Nervous System ...
In the HGB-206 Group C cohort, treatment with lovo-cel led to sustained production of anti-sickling hemoglobin and complete ... This results in the production of anti-sickling hemoglobin that decreases the proportion of sickle hemoglobin, thereby reducing ...
Algeria , Annona , Antifungal Agents/therapeutic use , Antioxidants/chemistry , Candida albicans , Flavonoids , Plant Extracts/ ... In vitro evaluation of anti-sickling activity of crude flavonoid extracted from Drepanoalpha® and their phytochemical profiling ...
New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Esther ... New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Esther ... Allosteric modifiers of haemoglobin as direct anti-sickling agents target the fundamental pathophysiological mechanism of ... Interactions of an Anti-Sickling Drug with Hemoglobin in Red Blood Cells from a Patient with Sickle Cell Anemia. Strader MB, ...
These researchers are developing a new anti-sickling agent that works by binding with the defective hemoglobin that causes ... Advanced Studies with 5HMF-Most Potent Anti-Sickling Agent. Sickle cell disease is an inherited condition with several forms, ... These researchers are developing a new anti-sickling agent that works by binding with the defective hemoglobin that causes ... Despite considerable effort, there has been little progress in the development of new antisickling agents that have efficacy ...
New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? Oder E, ... Interactions of an Anti-Sickling Drug with Hemoglobin in Red Blood Cells from a Patient with Sickle Cell Anemia Michael Brad ... Interactions of an Anti-Sickling Drug with Hemoglobin in Red Blood Cells from a Patient with Sickle Cell Anemia Michael Brad ... GBT440 is an α-subunit-specific modifying agent that has recently been reported to increase HbS oxygen binding affinity and ...
Furthermore, unravelling the mechanisms of the anti-sickling effects of these agents could well reveal fresh insights on the ... to discover newer anti-sickling agents using high throughput screening of drug libraries. Not only will the compounds provide ... significant effects at concentrations known to be non-toxic can be very rapidly approved for clinical trials as these agents ...
But if theres still some residual sickle hemoglobin in there it accesses an anti-sickling agent in a sense. Based upon the ... We worked with chemists to develop a more chemically stable agent that has a longer half-life, shelf life, so you can actually ... We were looking at a number of other agents and smaller subsets of patients to determine whether they might have some role. For ...
Antisickling Agents Preferred Concept UI. M0001501. Registry Number. 0. Scope Note. Agents used to prevent or reverse the ... Desickling Agents Narrower Concept UI. M0001502. Registry Number. 0. Terms. Desickling Agents Preferred Term Term UI T003036. ... Antisickling Agents Preferred Term Term UI T003035. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1977). ... Antisickling Agents. Tree Number(s). D27.505.954.502.135. Unique ID. D000986. RDF Unique Identifier. http://id.nlm.nih.gov/mesh ...
Antisickling Agents Preferred Concept UI. M0001501. Registry Number. 0. Scope Note. Agents used to prevent or reverse the ... Desickling Agents Narrower Concept UI. M0001502. Registry Number. 0. Terms. Desickling Agents Preferred Term Term UI T003036. ... Antisickling Agents Preferred Term Term UI T003035. Date01/01/1999. LexicalTag NON. ThesaurusID NLM (1977). ... Antisickling Agents. Tree Number(s). D27.505.954.502.135. Unique ID. D000986. RDF Unique Identifier. http://id.nlm.nih.gov/mesh ...
... consider also ANTISICKLING AGENTS. Allowable Qualifiers:. BL blood. CF cerebrospinal fluid. CI chemically induced. CL ...
The antisickling action of hydroxyurea is thought to be due to the induction of hemoglobin F, but it may also reduce neutrophil ... Considering the proposed mechanism of priapism in SCD patients, it may be a useful agent in the treatment of sickle-cell- ... preclude its use as a first-line agent. ...
Antineoplastic Agents. Antisickling Agents. Enzyme Inhibitors. Molecular Mechanisms of Pharmacological Action. Nucleic Acid ... previous or current treatment with HU or another anti-sickling drug; or abnormal transcranial Doppler ultrasound (TCD) velocity ...
See also Antisickling Agents Anemia, Splenic See Hypersplenism Anemias, Iron-Deficiency See Anemia, Iron-Deficiency ...
Furthermore, unravelling the mechanisms of the anti-sickling effects of these agents could well reveal fresh insights on the ... to discover newer anti-sickling agents using high throughput screening of drug libraries. Not only will the compounds provide ... significant effects at concentrations known to be non-toxic can be very rapidly approved for clinical trials as these agents ...
These infectious agents contribute to the large number of persons with cancer and the worrisome number that die from the ... antimalarial and anti-sickling properties. The safety profiles and suggestions for conservation of the Z. species were also ... These compounds are biosynthesized by plants as protection mechanisms against environmental factors and infectious agents. This ... resistance of Plasmodium species to many available antimalarials calls for a continuous search for newer antimalarial agents. ...
Anemia, Sickle Cell/diagnosis , Antisickling Agents , Bacteriological Techniques 3. Drépanocytose : Généralités, Enjeux, défis ...
assays for induction in red blood cell precursors of endogenous anti-sickling globin chains such as beta-like gamma-globin ( ... and provide inroads toward new agents for SCD treatments. The assays should be suitable to be candidates for screening in the ...
... agent alkylating agents alkylating agent therapies alkylating-agent therapies alkylating agent therapy alkylating-agent therapy ... antishivering anti-shivering antishock anti-shock antisialagogue antisialagogues antisialic antisialics antisickling anti-sickling ... agenize agenized agenizes agenizing agent agential agenting agentings agentive Agent Orange agent provocateur agents agents ... antivimentin anti-vimentin antivin antiviral anti-viral anti-viral agent antiviral agent anti-viral agents antiviral agents ...
  • ous extract obtained and used for antisickling assays. (who.int)
  • The purpose of this RFA is to fund the development and adaptation of biological assays for automated, high throughput screening of compounds that can potentially be used to improve the understanding of the biology of Sickle Cell Disease (SCD) and provide inroads toward new agents for SCD treatments. (nih.gov)
  • Quantitative effect of Hydroxyurea as anti-sickling agent in the molecular polymerization of the Sickle Cell Anemia is analyzed in this project. (fapesp.br)
  • One of the major challenges in finding effective therapeutic agents for the treatment of sickle cell disease has been the lack of agents that would specifically bind with the high concentration of intracellular HbS present in patients without causing adverse effects, and 5HMF appears to have promise in satisfying this condition. (nih.gov)
  • While we apply insights from the basic research to identify new therapeutic targets, the Thein lab is also involved in a project with Dr Bill Eaton (Laboratory of Chemical Physics, NIDDK/NIH) to discover newer anti-sickling agents using high throughput screening of drug libraries. (nih.gov)
  • of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (= 0.98 ≤ 0.001) negatively with fetal hemoglobin (HbF) levels (= ?0.558 = 0.027) negatively with pH (= ?0.688 = 0.026) negatively with pretreatment with the antisickling agent Aes-103 (5-hydroxymethyl-2-furfural) (= ?0.766 = 0.002) and positively with the presence of long intracellular materials while visualized by transmission electron microscopy (= 0.799 = 0.002). (biodiversityhotspot.org)
  • New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? (nih.gov)
  • In collaboration with the NHLBI Sickle Cell Disease Reference Laboratory, we have discovered a new potent and specific antisickling 5-membered aromatic scaffold, 5HMF. (nih.gov)
  • Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions. (nih.gov)
  • Not only will the compounds provide further insight on the sickling mechanisms, but those that show therapeutically significant effects at concentrations known to be non-toxic can be very rapidly approved for clinical trials as these agents are either already FDA-approved or under clinical development for other diseases. (nih.gov)
  • Furthermore, unravelling the mechanisms of the anti-sickling effects of these agents could well reveal fresh insights on the HbS fiber formation. (nih.gov)
  • The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology. (nih.gov)
  • These researchers are developing a new anti-sickling agent that works by binding with the defective hemoglobin that causes sickling. (nih.gov)
  • The antisickling action of hydroxyurea is thought to be due to the induction of hemoglobin F, but it may also reduce neutrophil and reticulocyte counts, thereby decreasing the interaction of sickle cells with vascular endothelium resulting in blood "trapping" and, thus, priapism. (medscape.com)
  • In collaboration with the NHLBI Sickle Cell Disease Reference Laboratory, we have discovered a new potent and specific antisickling 5-membered aromatic scaffold, 5HMF. (nih.gov)
  • One of the major challenges in finding effective therapeutic agents for the treatment of sickle cell disease has been the lack of agents that would specifically bind with the high concentration of intracellular HbS present in patients without causing adverse effects, and 5HMF appears to have promise in satisfying this condition. (nih.gov)
  • The purpose of this RFA is to fund the development and adaptation of biological assays for automated, high throughput screening of compounds that can potentially be used to improve the understanding of the biology of Sickle Cell Disease (SCD) and provide inroads toward new agents for SCD treatments. (nih.gov)
  • While we apply insights from the basic research to identify new therapeutic targets, the Thein lab is also involved in a project with Dr Bill Eaton (Laboratory of Chemical Physics, NIDDK/NIH) to discover newer anti-sickling agents using high throughput screening of drug libraries. (nih.gov)
  • New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo? (nih.gov)
  • Considering the proposed mechanism of priapism in SCD patients, it may be a useful agent in the treatment of sickle-cell-induced priapism. (medscape.com)
  • Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions. (nih.gov)
  • [ 22 ] As with diethylstilbestrol, hydroxyurea's adverse effects, as well as the lack of studies in patients less than 18 years of age, preclude its use as a first-line agent. (medscape.com)

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