ObjectiveTo obtain multicentre data on the prevalence of normal, high or conditional (intermediat... more ObjectiveTo obtain multicentre data on the prevalence of normal, high or conditional (intermediate) blood velocity in the cerebral arteries among children with sickle cell disease (SCD) in Nigeria.DesignA prospective observational study in five tertiary healthcare institutions. By transcranial Doppler (TCD) ultrasonography, cerebral artery peak systolic blood velocity (PSV) was determined in 193 children with SCD and time averaged mean of the maximum blood velocity (TAMMV) in a different cohort of 115 children. This design was to make the findings relevant to hospitals with TCD equipment that measure either PSV or TAMMV.SettingNigeria.Participants308 children (126 girls, 182 boys; age 2–16 years).Main outcome measuresPercentage of children with SCD who have normal, high or intermediate (often termed conditional) PSV or TAMMV.ResultsIn the cohort of 193 children, PSV was normal in 150 (77.7%), high in 7 (3.6%) and conditional in 36 (18.7%). In the cohort of 115 children, TAMMV was no...
Journal of BioMedical Research and Clinical Practice, 2019
Vaso-occlusion in sickle cell anaemia (SCA) is mediated via increased expression of adhesion mole... more Vaso-occlusion in sickle cell anaemia (SCA) is mediated via increased expression of adhesion molecules. Micro-RNA 466i up regulates the expression of interleukin-10 and may contribute to the pathogenesis of the complications in SCA. We sought to investigate the relationship between changes in the level of micro-RNA 466i and the frequency of vaso-occlusive complications in SCA patients. Red blood cells were lysed using ammonium chloride. The resulting white blood cell pellets were lysed in guanidiumisothiocyanate (GITC) lyses buffer. From the GITC lysate, total RNA was extracted. Thereafter, the amount of micro-RNA 466i was quantified. There were no relationships between microRNA 466i and the frequency of complications in SCA patients. (p=0.066) There was also no significant difference in the levels of micro-RNA 466i between patients who had vaso-occlusive complications and those that did not.(p=0.9307) Micro-RNA 466i increased with age (p=0.03) but there was no significant differenc...
Introduction: Whereas several studies show that homozygous (HbSS) sickle cell disease protects ag... more Introduction: Whereas several studies show that homozygous (HbSS) sickle cell disease protects against human immunodeficiency virus infection, it is not clear if human immunodeficiency virus infection is affected by the heterozygous state of the sickle globin gene (HbAS or sickle cell trait). Objective: To evaluate the effects of sickle cell trait on the prevalence and severity of human immunodeficiency virus type 1 infection in a large patient population. Methods: Hemoglobin genotype was determined by high performance liquid chromatography (HPLC) in 1,226 HIV-1 patients in Nigeria. Their demographic data were documented. Blood CD4+ cell counts and HIV-1 viral load previously determined on the same blood samples to guide clinical care were used as indices of severity of HIV-1 infection. Statistical analysis of the data was done to evaluate the effects of sickle cell trait on the severity and prevalence of HIV-1 infection, relative to the prevalence of 1.4% in the general population ...
Background and Novel Aspect of this Work: In the light of previous findings that inflammation pre... more Background and Novel Aspect of this Work: In the light of previous findings that inflammation predisposes to intercellular adhesion and microvascular occlusion in sickle cell disease (SCD), this study investigated the relationship between the number of vaso-occlusive events in SCD, plasma levels of the pro-inflammatory molecules 12-Hydroxyeicosatetraenoic acid (12-HETE), TNF-α and IL-1β; and single nucleotide polymorphisms (SNPs) in the gene 12-Lipooxygenase (ALOX-12), which encodes the enzyme 12-Lipoxygenase that catalyzes the biosynthesis of 12-HETE.Objective: To evaluate the relationship between vaso-occlusion in SCD and plasma concentrations of 12-HETE, TNF-α, and IL-1β; and single nucleotide polymorphisms (SNPs) in ALOX-12 gene.Participants and Methods: In 50 HbSS patients, the numbers of vaso-occlusive crisis requiring hospital treatment in the previous 1 year and the vaso-occlusive complications of SCD developed to date (e.g stroke) were added to obtain the vaso-occlusive eve...
OBJECTIVE The purpose of this pilot study was to explore the effect of omega-3 fatty acids and po... more OBJECTIVE The purpose of this pilot study was to explore the effect of omega-3 fatty acids and potassium thiocyanate on conditional peak systolic cerebral artery blood velocity in children with sickle cell anemia (SCA). METHODS Transcranial doppler ultrasonography (TCD) was done on 232 SCA children, and 21 found with conditional peak systolic blood velocity (PSV) of 200-249 cm/s in internal carotid, middle or anterior cerebral arteries. These were randomized to receive omega-3 fatty acids and potassium thiocyanate with standard treatment of SCA (test group, N = 14), or standard treatment only (control group, N = 7). After 3 months of treatment, PSV was measured again. RESULTS Right middle cerebral artery PSV was significantly reduced in the test relative to the control groups (p = 0.04). PSV returned to normal in 79% of the test versus 43% of the control group; and increased to abnormal in one member of the control group, but none of the test group. CONCLUSIONS The pilot data suggest that in SCA, omega-3 fatty acids and potassium thiocyanate might reduce conditional blood velocity to normal, or prevent progression to abnormal values. A larger, randomized, clinical trial is required to further address the current gap in management of conditional TCD blood velocity.
Prostate cancer is a significant public health problem affecting men globally. In 2018, it was th... more Prostate cancer is a significant public health problem affecting men globally. In 2018, it was the second most commonly diagnosed cancer among men world-wide and disproportionately impact men of African ancestry. Some of the modifiable risk factors for prostate cancer include knowledge and attitudes about the disease, the belief system of individuals and their diet. Moreover, physical activity, alcohol and tobacco consumption have also been suggested as behavioral factors that contribute to prostate cancer disparities. This study compares modifiable risk factors implicated in prostate cancer among men living in Africa and African immigrants living in the United States to identifying behavioral factors that can be targeted for intervention. A cross-sectional study design was employed among Black men in Nigeria, Cameroon and African immigrants in United States using the Global Prostate Cancer Measure for Black men. Findings indicate that Nigerian and Cameroonian men residing in the Un...
Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also fr... more Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also from other genetic and environmental factors acting in concert. The biological basis of individual variation in the severity of SCD is not fully understood. Our previous study revealed that WBCs from people with severe SCD express high levels of the adhesion molecules L-selectin (CD62L) and αMβ2 integrin (CD11a/18) in steady state. These cell membrane proteins mediate leukocyte adherence to vascular endothelium and facilitate vaso-occlusion: a fundamental pathological process in SCD. The lipid composition of cell membranes affects the level of expression of adhesion molecules on the membrane, its structural integrity and function. Abnormalities of plasma and erythrocyte lipids in SCD had been recognised. However, there is little information on lipid composition of leukocyte and platelet membranes in SCD, and its relationship with clinical severity. Objectives: To analyse the membrane fatty...
In a previous study, we observed that high expression of the adhesion molecules L-selectin and αM... more In a previous study, we observed that high expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocyte membranes is associated with severe sickle cell disease (Eur J Haem.2002; 69: 135 – 144). The lipid composition of cell membranes affects adhesion molecule expression, cell integrity and function (Calder P Lipids.2003; 38: 343–352). Omega-3 fatty acids (FA) such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) are vital for the structure and function of cell membranes. Sickling perturbs the normal asymmetry of erythrocyte membrane lipids. Choline phosphoglycerides (CPG) move from the outer to inner leaflet. Ethanolamine (EPG) and serine (SPG) phosphoglycerides shift from the inner to the outer layer. Exposure of the highly reactive SPG to plasma promotes clotting, rbc adhesion to vascular endothelium, wbcs and platelets; vaso-occlusion, and ischaemic organ damage. Loss of lipid asymmetry impairs the structure of rbc membranes, causes abnormal ion flux and exac...
Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozyg... more Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozygous sickle cell disease (SCD), and treatment with n-3 fatty acids (FA) is beneficial to affected individuals (Tomer et al, Thromb Haemost2001; 966–974). Phosphatidylserine has a role in sickle erythrocyte-endothelial adhesion, which contributes to vessel occlusion in SCD (Setty et al, Blood2002; 1564–1571). Considering that n-3 and n-6 FA are essential structural and functional components of the red cell membrane, the objective of this study was to find out if abnormalities of these FA affect the degree of anaemia in SCD. We recruited 43 HbSS patients and 43 racially-matched, healthy, HbAA controls living in the same environment; analysed the fatty acid composition of erythrocyte membrane choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and sought for relationship between steady-state Hb level in SCD and the proportion of n-3 FA in the red cel...
Introduction The severity of sickle cell disease (SCD) increases with absolute neutrophil count (... more Introduction The severity of sickle cell disease (SCD) increases with absolute neutrophil count (ANC, Eur J Haematol. 1998; 60: 267-8) and expression of adhesion molecules by leukocytes (Eur J Haematol. 2002; 69: 135 -144.). Intercellular adhesion molecule 1 (ICAM 1) on vascular endothelium mediates leukocyte adherence to the blood vessel wall. This contributes to vaso-occlusion, the main mechanism of tissue damage in SCD. Micro-RNA 221 (MIR 221) regulates the gene for ICAM-1 (J Cell Science 2011; 124, 999-1006). How the severity of SCD relates with expression of MIR 221 was evaluated in this study. Methods Following IRB approval and informed consent by appropriate persons, 25 healthy HbAA control persons and 73 HbSS patients (45M, 28F; age 2-18 yrs) were consecutively enrolled from University of Nigeria Teaching Hospital, Enugu. Patients who had blood transfusion in the previous 3 months were excluded. Information from medical records and clinical assessment was used to determine t...
1624 Background and Study Objectives. Previous studies showed that: (1) increased blood levels of... more 1624 Background and Study Objectives. Previous studies showed that: (1) increased blood levels of the omega-3 (n3) fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with increased steady-state Hb levels and reduced prevalence of the complications of sickle cell disease (SCD); (2) EPA and DHA reduced the number of crisis in a pilot group of 5 HbSS patients. The primary aim of this study was to assess the effects of EPA and DHA in a larger number of patients. SCD causes recurrent vaso-occlusion, ischemia-reperfusion injury and inflammation (Osarogiagbon et al. Blood. 2000, 96: 314–320). A metabolite of DHA (10,17S-docosatriene) protects against ischemia-reperfusion injury by inhibiting leukocyte infiltration and expression of pro-inflammatory genes (Marcheselli et al, J Bio Chem. 2003; 278: 43807–43817. Our hypothesis was that anti-inflammatory properties contribute to the mechanism(s) of action of DHA/EPA in SCD. The secondary objective was to...
Lecithin cholesterol acyltransferase (LCAT) activity and free cholesterol and cholesterol ester c... more Lecithin cholesterol acyltransferase (LCAT) activity and free cholesterol and cholesterol ester concentrations were determined in serum samples from 28 patients with acute lymphoblastic leukemia (ALL) and in an equal number of healthy controls. No significant alterations in LCAT activity, free cholesterol, or esterified cholesterol levels were observed in the ALL patients compared with the controls.
ObjectiveTo obtain multicentre data on the prevalence of normal, high or conditional (intermediat... more ObjectiveTo obtain multicentre data on the prevalence of normal, high or conditional (intermediate) blood velocity in the cerebral arteries among children with sickle cell disease (SCD) in Nigeria.DesignA prospective observational study in five tertiary healthcare institutions. By transcranial Doppler (TCD) ultrasonography, cerebral artery peak systolic blood velocity (PSV) was determined in 193 children with SCD and time averaged mean of the maximum blood velocity (TAMMV) in a different cohort of 115 children. This design was to make the findings relevant to hospitals with TCD equipment that measure either PSV or TAMMV.SettingNigeria.Participants308 children (126 girls, 182 boys; age 2–16 years).Main outcome measuresPercentage of children with SCD who have normal, high or intermediate (often termed conditional) PSV or TAMMV.ResultsIn the cohort of 193 children, PSV was normal in 150 (77.7%), high in 7 (3.6%) and conditional in 36 (18.7%). In the cohort of 115 children, TAMMV was no...
Journal of BioMedical Research and Clinical Practice, 2019
Vaso-occlusion in sickle cell anaemia (SCA) is mediated via increased expression of adhesion mole... more Vaso-occlusion in sickle cell anaemia (SCA) is mediated via increased expression of adhesion molecules. Micro-RNA 466i up regulates the expression of interleukin-10 and may contribute to the pathogenesis of the complications in SCA. We sought to investigate the relationship between changes in the level of micro-RNA 466i and the frequency of vaso-occlusive complications in SCA patients. Red blood cells were lysed using ammonium chloride. The resulting white blood cell pellets were lysed in guanidiumisothiocyanate (GITC) lyses buffer. From the GITC lysate, total RNA was extracted. Thereafter, the amount of micro-RNA 466i was quantified. There were no relationships between microRNA 466i and the frequency of complications in SCA patients. (p=0.066) There was also no significant difference in the levels of micro-RNA 466i between patients who had vaso-occlusive complications and those that did not.(p=0.9307) Micro-RNA 466i increased with age (p=0.03) but there was no significant differenc...
Introduction: Whereas several studies show that homozygous (HbSS) sickle cell disease protects ag... more Introduction: Whereas several studies show that homozygous (HbSS) sickle cell disease protects against human immunodeficiency virus infection, it is not clear if human immunodeficiency virus infection is affected by the heterozygous state of the sickle globin gene (HbAS or sickle cell trait). Objective: To evaluate the effects of sickle cell trait on the prevalence and severity of human immunodeficiency virus type 1 infection in a large patient population. Methods: Hemoglobin genotype was determined by high performance liquid chromatography (HPLC) in 1,226 HIV-1 patients in Nigeria. Their demographic data were documented. Blood CD4+ cell counts and HIV-1 viral load previously determined on the same blood samples to guide clinical care were used as indices of severity of HIV-1 infection. Statistical analysis of the data was done to evaluate the effects of sickle cell trait on the severity and prevalence of HIV-1 infection, relative to the prevalence of 1.4% in the general population ...
Background and Novel Aspect of this Work: In the light of previous findings that inflammation pre... more Background and Novel Aspect of this Work: In the light of previous findings that inflammation predisposes to intercellular adhesion and microvascular occlusion in sickle cell disease (SCD), this study investigated the relationship between the number of vaso-occlusive events in SCD, plasma levels of the pro-inflammatory molecules 12-Hydroxyeicosatetraenoic acid (12-HETE), TNF-α and IL-1β; and single nucleotide polymorphisms (SNPs) in the gene 12-Lipooxygenase (ALOX-12), which encodes the enzyme 12-Lipoxygenase that catalyzes the biosynthesis of 12-HETE.Objective: To evaluate the relationship between vaso-occlusion in SCD and plasma concentrations of 12-HETE, TNF-α, and IL-1β; and single nucleotide polymorphisms (SNPs) in ALOX-12 gene.Participants and Methods: In 50 HbSS patients, the numbers of vaso-occlusive crisis requiring hospital treatment in the previous 1 year and the vaso-occlusive complications of SCD developed to date (e.g stroke) were added to obtain the vaso-occlusive eve...
OBJECTIVE The purpose of this pilot study was to explore the effect of omega-3 fatty acids and po... more OBJECTIVE The purpose of this pilot study was to explore the effect of omega-3 fatty acids and potassium thiocyanate on conditional peak systolic cerebral artery blood velocity in children with sickle cell anemia (SCA). METHODS Transcranial doppler ultrasonography (TCD) was done on 232 SCA children, and 21 found with conditional peak systolic blood velocity (PSV) of 200-249 cm/s in internal carotid, middle or anterior cerebral arteries. These were randomized to receive omega-3 fatty acids and potassium thiocyanate with standard treatment of SCA (test group, N = 14), or standard treatment only (control group, N = 7). After 3 months of treatment, PSV was measured again. RESULTS Right middle cerebral artery PSV was significantly reduced in the test relative to the control groups (p = 0.04). PSV returned to normal in 79% of the test versus 43% of the control group; and increased to abnormal in one member of the control group, but none of the test group. CONCLUSIONS The pilot data suggest that in SCA, omega-3 fatty acids and potassium thiocyanate might reduce conditional blood velocity to normal, or prevent progression to abnormal values. A larger, randomized, clinical trial is required to further address the current gap in management of conditional TCD blood velocity.
Prostate cancer is a significant public health problem affecting men globally. In 2018, it was th... more Prostate cancer is a significant public health problem affecting men globally. In 2018, it was the second most commonly diagnosed cancer among men world-wide and disproportionately impact men of African ancestry. Some of the modifiable risk factors for prostate cancer include knowledge and attitudes about the disease, the belief system of individuals and their diet. Moreover, physical activity, alcohol and tobacco consumption have also been suggested as behavioral factors that contribute to prostate cancer disparities. This study compares modifiable risk factors implicated in prostate cancer among men living in Africa and African immigrants living in the United States to identifying behavioral factors that can be targeted for intervention. A cross-sectional study design was employed among Black men in Nigeria, Cameroon and African immigrants in United States using the Global Prostate Cancer Measure for Black men. Findings indicate that Nigerian and Cameroonian men residing in the Un...
Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also fr... more Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also from other genetic and environmental factors acting in concert. The biological basis of individual variation in the severity of SCD is not fully understood. Our previous study revealed that WBCs from people with severe SCD express high levels of the adhesion molecules L-selectin (CD62L) and αMβ2 integrin (CD11a/18) in steady state. These cell membrane proteins mediate leukocyte adherence to vascular endothelium and facilitate vaso-occlusion: a fundamental pathological process in SCD. The lipid composition of cell membranes affects the level of expression of adhesion molecules on the membrane, its structural integrity and function. Abnormalities of plasma and erythrocyte lipids in SCD had been recognised. However, there is little information on lipid composition of leukocyte and platelet membranes in SCD, and its relationship with clinical severity. Objectives: To analyse the membrane fatty...
In a previous study, we observed that high expression of the adhesion molecules L-selectin and αM... more In a previous study, we observed that high expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocyte membranes is associated with severe sickle cell disease (Eur J Haem.2002; 69: 135 – 144). The lipid composition of cell membranes affects adhesion molecule expression, cell integrity and function (Calder P Lipids.2003; 38: 343–352). Omega-3 fatty acids (FA) such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) are vital for the structure and function of cell membranes. Sickling perturbs the normal asymmetry of erythrocyte membrane lipids. Choline phosphoglycerides (CPG) move from the outer to inner leaflet. Ethanolamine (EPG) and serine (SPG) phosphoglycerides shift from the inner to the outer layer. Exposure of the highly reactive SPG to plasma promotes clotting, rbc adhesion to vascular endothelium, wbcs and platelets; vaso-occlusion, and ischaemic organ damage. Loss of lipid asymmetry impairs the structure of rbc membranes, causes abnormal ion flux and exac...
Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozyg... more Previous studies indicate that perturbation of erythrocyte and/or plasma lipids occurs in homozygous sickle cell disease (SCD), and treatment with n-3 fatty acids (FA) is beneficial to affected individuals (Tomer et al, Thromb Haemost2001; 966–974). Phosphatidylserine has a role in sickle erythrocyte-endothelial adhesion, which contributes to vessel occlusion in SCD (Setty et al, Blood2002; 1564–1571). Considering that n-3 and n-6 FA are essential structural and functional components of the red cell membrane, the objective of this study was to find out if abnormalities of these FA affect the degree of anaemia in SCD. We recruited 43 HbSS patients and 43 racially-matched, healthy, HbAA controls living in the same environment; analysed the fatty acid composition of erythrocyte membrane choline (CPG), serine (SPG) and ethanolamine (EPG) phosphoglycerides and sphingomyelin (SPM); and sought for relationship between steady-state Hb level in SCD and the proportion of n-3 FA in the red cel...
Introduction The severity of sickle cell disease (SCD) increases with absolute neutrophil count (... more Introduction The severity of sickle cell disease (SCD) increases with absolute neutrophil count (ANC, Eur J Haematol. 1998; 60: 267-8) and expression of adhesion molecules by leukocytes (Eur J Haematol. 2002; 69: 135 -144.). Intercellular adhesion molecule 1 (ICAM 1) on vascular endothelium mediates leukocyte adherence to the blood vessel wall. This contributes to vaso-occlusion, the main mechanism of tissue damage in SCD. Micro-RNA 221 (MIR 221) regulates the gene for ICAM-1 (J Cell Science 2011; 124, 999-1006). How the severity of SCD relates with expression of MIR 221 was evaluated in this study. Methods Following IRB approval and informed consent by appropriate persons, 25 healthy HbAA control persons and 73 HbSS patients (45M, 28F; age 2-18 yrs) were consecutively enrolled from University of Nigeria Teaching Hospital, Enugu. Patients who had blood transfusion in the previous 3 months were excluded. Information from medical records and clinical assessment was used to determine t...
1624 Background and Study Objectives. Previous studies showed that: (1) increased blood levels of... more 1624 Background and Study Objectives. Previous studies showed that: (1) increased blood levels of the omega-3 (n3) fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with increased steady-state Hb levels and reduced prevalence of the complications of sickle cell disease (SCD); (2) EPA and DHA reduced the number of crisis in a pilot group of 5 HbSS patients. The primary aim of this study was to assess the effects of EPA and DHA in a larger number of patients. SCD causes recurrent vaso-occlusion, ischemia-reperfusion injury and inflammation (Osarogiagbon et al. Blood. 2000, 96: 314–320). A metabolite of DHA (10,17S-docosatriene) protects against ischemia-reperfusion injury by inhibiting leukocyte infiltration and expression of pro-inflammatory genes (Marcheselli et al, J Bio Chem. 2003; 278: 43807–43817. Our hypothesis was that anti-inflammatory properties contribute to the mechanism(s) of action of DHA/EPA in SCD. The secondary objective was to...
Lecithin cholesterol acyltransferase (LCAT) activity and free cholesterol and cholesterol ester c... more Lecithin cholesterol acyltransferase (LCAT) activity and free cholesterol and cholesterol ester concentrations were determined in serum samples from 28 patients with acute lymphoblastic leukemia (ALL) and in an equal number of healthy controls. No significant alterations in LCAT activity, free cholesterol, or esterified cholesterol levels were observed in the ALL patients compared with the controls.
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