Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments

Publication date: Available online 2 November 2019Source: Nitric OxideAuthor(s): Luis E.F. Almeida, Sayuri Kamimura, Celia M. de Souza Batista, Nicholas Spornick, Margaret Y. Nettleton, Elizabeth Walek, Meghann L. Smith, Julia Finkel, Deepika Darbari, Paul Wakim, Zenaide M.N. QuezadoAbstractThe hypothesis of decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD) proposes that multiple factors leading to decreased NO production and increased consumption contributes to vaso-occlusion, pulmonary hypertension, and pain. The anion nitrite is central to NO physiology as it is an end product of NO metabolism and serves as a reservoir for NO formation. However, there is little data on nitrite levels in SCD patients and its relationship to pain phenotype. We measured nitrite in SCD subjects and examined its relationship to SCD pain. In SCD subjects, median whole blood, red blood cell and plasma nitrite levels were higher than in controls, and were not associated with pain burden. Similarly, Townes and BERK homozygous SCD mice had elevated blood nitrite. Additionally, in red blood cells and plasma from SCD subjects and in blood and kidney from Townes homozygous mice, levels of cyclic guanosine monophosphate (cGMP) were higher compared to controls. In vitro, hemoglobin concentration, rather than sickle hemoglobin, was responsible for nitrite metabolism rate. In vivo, inhibition of NO synthases and xanthine oxidoreductase decreased nitrite levels in homozygotes but not ...
Source: Nitric Oxide - Category: Chemistry Source Type: research

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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
In conclusion, high baPWV accompanied by hypertension could increase the risk of cardio-cerebrovascular events. The predictive value of baPWV combined with BP on cardio-cerebrovascular events is superior compared with that of either baPWV or BP alone. PMID: 31807146 [PubMed]
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
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Source: Journal of Medicine and Life - Category: General Medicine Tags: J Med Life Source Type: research
Abstract Sickle cell disease (SCD) is among the most common genetic diseases in the United States, affecting approximately 100,000 people. In the United States, SCD is characterized by a shortened life expectancy of only about 50 years in severe subtypes, significant quality-of-life impairments, and increased healthcare utilization and spending. SCD is characterized by chronic hemolytic anemia, vaso-occlusion, and progressive vascular injury affecting multiple organ systems. The pathophysiology is directly related to polymerization of deoxygenated hemoglobin, leading to a cascade of pathologic events including ery...
Source: The American Journal of Managed Care - Category: Health Management Authors: Tags: Am J Manag Care Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Novel or Improved Approaches To Treating Sickle Cell Disease Source Type: research
ConclusionsThis is the first report describing prevalence of SCD-related complications in the MU-SCD Cohort. We identified this population to have an increasing frequency of hemolytic complications and sickle cell nephropathy with advancing age. Onset of persistent proteinuria occurred in the second decade of life, followed by renal insufficiency or end stage renal disease in subsequent decades. As previously demonstrated in the Cooperative Study of Sickle Cell Disease and the Jamaican SCD Cohort study, renal insufficiency was a significant risk factor for early mortality. Further studies are required for identification of...
Source: Blood - Category: Hematology Authors: Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
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Source: European Journal of Pediatrics - Category: Pediatrics Source Type: research
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Source: Clinical Hemorheology and Microcirculation - Category: Hematology Authors: Tags: Clin Hemorheol Microcirc Source Type: research
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Source: International Journal of Nursing Studies - Category: Nursing Authors: Tags: Cochrane Nursing Care Field (CNCF) – Cochrane Review Summary Source Type: research
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