Department of Physiology

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    Peripheral sensory neuropathy is associated with circulating angiopoietins in type 2 diabetes patients in Ghana
    (Journal of Clinical & Translational Endocrinology, 2023) Agyekum, J.A.; Yeboah, K.
    Objective: Peripheral sensory neuropathy (PSN) is a common complication of type 2 diabetes (T2DM) that can lead to frequent ulcerations, lower extremities, and reduced quality of life. Imbalance in the circulating levels of angiogenic growth factors, notably, angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) may be among the underlying mechanisms of PSN in T2DM patients. We studied the association between PSN and angiogenic growth factors, Ang-1, Ang-2 and VEGF in T2DM patients in Ghana. Methods: In a case-control study design, PSN was evaluated in 160 patients with T2DM and 108 nondiabetic controls using vibration perception threshold (VPT) and diabetic neurological examination (DNE). The definition of PSN was abnormal VPT (≥25 mV) or the presence of neuropathic symptoms on examination (DNE score > 3). In addition, fasting venous blood samples were collected to measure circulating levels of Ang-1, Ang-2 and VEGF. Results: Compared to non-diabetic controls, patients with T2DM had a higher prevalence of PSN using abnormal VPT (20.6 % vs 2.8 %, p < 0.001) or neuropathic symptoms (35.6 % vs 3.7 %, p < 0.001). Compared to nondiabetic controls, patients with T2DM had increased levels of Ang-2 [597 (274 – 1005) vs 838 (473 – 1241) ng/ml, p = 0.018] and VEGF [48.4 (17.4 – 110.1) vs 72.2 (28 – 201.8), p = 0.025] and decreased Ang-1 levels [41.1 (30 – 57.3) vs 36.1 (24.7 – 42.1) ng/ml, p = 0.01]. In regression analyses, an increase in Ang-1 levels was associated with decreased odds, while an increase in Ang-2 levels was associated with increased odds, of abnormal VPT and neuropathic symptoms in T2DM patients. Conclusion: In our study population, PSN was associated with reduced plasma levels of Ang-1 and increased plasma levels of Ang-2 in patients with T2DM. Therefore, an imbalance of angiopoietins may be associated with PSN in T2DM.
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    Association between eNOS Gene Polymorphism (T786C and VNTR) and Sickle Cell Disease Patients in Ghana
    (Diseases, 2018) Antwi-Boasiako, C.; Dzudzor, B.; Doku, A.; et al.
    Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in Ghana and several other African countries. The current study aimed to determine a possible association between variants of the eNOS gene (variable number of tandem repeats in intron 4 and T786C) in SCD complications among Ghanaian patients. This was a cross-sectional study involving 89 HbSS patients with complications and 46 HbSS patients without complications. Genomic DNA was extracted from leukocytes in the buffy coat and separated from collected whole blood samples of the study participants. PCR amplification, followed by restriction fragment length polymorphism (RFLP) was used to genotype T786C (rs2070744) variants. Variable number of tandem repeats (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a significant difference in the genotype frequency of the T786C variant between HbSS patients with complications and those without complications (p = 0.0165). However, there was no significant difference in the VNTR intron 4 variant of the eNOS gene between patients with complications and those without complications (p > 0.05). The study shows an association between the eNOS gene variant (T786C) and complications in SCD.
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    Correlation of lipid peroxidation and nitric oxide metabolites, trace elements, and antioxidant enzymes in patients with sickle cell disease
    (Journal of Clinical Laboratory Analysis, 2020-02-17) Antwi-Boasiako, C.; Dankwah, G.B.; Aryee, R.; Hayfron-Benjamin, C.; Aboagye, G.; Campbell, A.D.
    Background: Lipid peroxidation plays a very important role in sickle cell pathophysiology. The formation of malondialdehyde (MDA) in patients with sickle cell disease (SCD) may lead to endothelial dysfunction. Nitric oxide (NO) is a known vasodilator which plays a role in endothelial function. The current study determined the association between MDA and NO metabolites (NOx), trace elements, and antioxidant enzymes (SOD and CAT) in patients with SCD. The ratio of MDA/NOx was also determined as an index of oxidative stress in the study groups. Methods: This was a cross-sectional study involving 90 patients with SCD and 50 “healthy” controls. Blood samples (n = 140) were collected from the study groups. The plasma, sera, and red cells were kept at −20°C for biochemical analyses. Hemoglobin (Hb) and NOx levels were determined in the plasma using Labsystem Multiskan MS and Griess reagent system, respectively. Super oxide dismutase (SOD) and catalase (CAT) levels were determined in the red cells using assay kits from Cayman chemicals. Lipid peroxidation biomarker MDA was determined in the sera using the TBARS assay. Levels of iron (Fe), copper (Cu), and zinc (Zn) were also determined in the sera using Variant 240FS. MDA and NOx ratio was computed for the study groups and compared. Results: Levels of Hb, NOx, SOD, CAT, and Zn were significantly lower in the patients with SCD (P < .001). MDA, Fe, and MDA/ NOx ratio were, however, significantly higher in the patients with SCD (P < .001). There was no significant correlation between MDA and NOx, SOD, CAT, Fe, and Zn in the study groups. MDA, however, correlated positively and significantly with Cu in the HbSS patients with vaso-occlusive crises (VOC). Gender did not affect the levels of oxidative stress markers. Conclusions: Findings from this study suggest a link between lipid peroxidation and Cu in HbSS patients with VOC. Increased MDA/NOx ratio may contribute to sickle cell pathophysiology by promoting oxidative stress
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    Serum Potassium, Sodium, and Chloride Levels in Sickle Cell Disease Patients and Healthy Controls: A Case-Control Study at Korle-Bu Teaching Hospital, Accra
    (Biomarker Insights , 2019-08-13) Antwi-Boasiako, C.; Kusi-Mensah, Y.A.; Hayfron-Benjamin, C.; Aryee, R.; Dankwah, G.B.; Abla, K.L.; Darkwa, E.O.; Botchway, F.A.; Sampene-Donkor, E.
    The activity of Na+-K+ ATPase is altered in sickle cell disease (SCD), which affects serum electrolyte levels. This alteration is associated with several complications in sickle cell patients. This study evaluated the serum levels of sodium, potassium, and chloride in patients with SCD. The study was a case-control cross-sectional study involving 120 SCD patients in the steady state and 48 ‘healthy’ controls. The SCD patients were made up of 69 HbSS patients and 41 HbSC patients. Serum electrolyte levels (Na+, K+, and Cl−) were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS; Varian Australia Pty Ltd). Serum sodium levels were significantly lower in the sickle cell patients, compared with their ‘healthy’ counterparts (P = .0001). Although the study found significantly higher serum levels of potassium in the SCD patients (P = .0001), there was no significant difference in serum chloride levels between patients with SCD and the controls (P = .098). Serum sodium and chloride levels were not significantly different in both HbSS and HbSC patients (P = .197 and P = .553, respectively). The level of serum potassium in the HbSS patients was, however, significantly higher compared with those with the HbSC genotype (P = .0001). There is higher efflux of K+ from the intracellular into the extracellular space in HbSS patients, which may lead to red cell membrane dysfunction and associated complications.
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    Sickle Cell Disease: Reappraisal of the Role of Foetal Haemoglobin Levels in the Frequency of Vaso-Occlusive Crisis
    (Ghana Medical Journal, 2015-06) Antwi-Boasiako, C.; Frimpong, E.; Ababio, G.K.; Dzudzor, B.; Ekem, I.; Gyan, B.; Sodzi-Tettey, N.A.; Antwi, D.A.
    Background: Foetal haemoglobin has been implicated in the modulation of sickle cell crisis. Its level is generally inversely proportional to the severity of sickle cell disease (SCD) for a given sickle cell phenotypes. The main aim of therapy for vaso-occlusive crisis (VOC), which is the hallmark of SCD, is to reduce the chances of sickling through the prevention of polymerization of HbS. One way of preventing this polymerization is by increasing foetal haemoglobin levels. Objectives: To determine the relationship between HbF levels and the frequency of crisis in SCD patients in Ghana. Method: A longitudinal retrospective survey covering a period of 30 months was carried out on adult SCD patients at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. Results: Eighty-three adults aged 15 to 65 years made up of 40 males and 43 femalea were studied. Analysis of variance (ANOVA) gave significant results in Hb and HbF levels. Higher HbF levels were positively related to less frequent crisis and were significantly high in SCD patients than in controls. HbF effects on the clinical manifestations on SCD were variable. Conclusion: Threshold values of HbF play a role in reducing the frequency of vaso-occlusive crisis in SCD patients and this finding contributes to the body of available literature on SCD severity. However our work does not give the apparent threshold level of helpful HBF Level in SCD.
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    Total Serum Magnesium Levels and Calcium-To-Magnesium Ratio in Sickle Cell Disease
    (Medicina, 2019-08-27) Antwi-Boasiako, C.; Kusi-Mensah, Y.A.; Hayfron-Benjamin, C.; Aryee, R.; Dankwah, G.B.; Kwawukume, L.A.; Darkwa, E.O.
    Background and Objectives: Imbalance of calcium/magnesium ratio could lead to clinical complications in sickle cell disease (SCD). Low levels of magnesium have been associated with sickling, increased polymerization and vaso-occlusion (VOC) in sickle cell due to cell dehydration. The K-Cl cotransport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. The study evaluated total serum magnesium levels and computed calcium/magnesium ratio in SCD patients and “healthy” controls. Materials and Methods: The study was a case-control cross-sectional one, involving 120 SCD patients (79 Haemoglobin SS (HbSS)and 41 Haemoglobin SC (HbSC)) at the steady state and 48 “healthy” controls. Sera were prepared from whole blood samples (n = 168) and total magnesium and calcium measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd., Melbourne, VIC, Australia). Calcium/magnesium ratios were calculated in patients and the controls. Results: The prevalence of hypomagnesemia and hypocalcaemia among the SCD patients was observed to be 39.17% and 52.50% respectively, higher than the controls (4.17% and 22.92%, for hypomagnesemia and hypocalcaemia, respectively). Level of magnesium was significantly lower in the SCD patients compared to their healthy counterparts (p = 0.002). The magnesium level was further reduced in the HbSS patients but not significantly di erent from the HbSC patients (p = 0.584). calcium/magnesium ratio was significantly higher in the SCD patients (p = 0.031). Although calcium/magnesium ratio was higher in the HbSC patients compared to those with the HbSS genotype, the di erence was not significant (p = 0.101). Conclusion: The study shows that magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Although calcium/magnesium ratio is significantly higher in SCD patients compared with controls, there is no significant di erence between patients with HbSS and HbSC genotypes. Magnesium supplementation may be required in sickle cell patients.
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    Serum iron levels and copper-to-zinc ratio in sickle cell disease
    (Medicina (Lithuania), 2019-05-16) Antwi-Boasiako, C.; Dankwah, G.B.; Aryee, R.; Hayfron-Benjamin, C.; Doku, A.; N’guessan, B.B.; Asiedu-Gyekye, I.J.; Campbell, A.D.
    Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and "healthy" controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA "healthy" controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their "healthy" counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.
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    Low nitric oxide level is implicated in sickle cell disease and its complications in Ghana
    (Vascular Health and Risk Management, 2018-09) Antwi-Boasiako, C.; Campbell, A.D.
    Background: Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent clinical and experimental data suggest that NO may play a role in the pathogenesis and therapy of sickle cell disease (SCD). The aim of this study was to determine NO metabolites (NOx) in SCD patients at steady state and in vaso-occlusive crisis (VOC), as well as those with hemolytic clinical sub-phenotype that includes leg ulcers and priapism. Methodology: This was a case–control cross-sectional study conducted on a total of 694 subjects including 148 comparison group HbAA, 208 HbSS SCD patients in steady state, 82 HbSC SCD patients in steady state, 156 HbSS SCD patients in VOC, 34 HbSC SCD patients in VOC, 34 HbSS SCD patients in post VOC, 21 HbSS SCD patients with leg ulcer and 11 HbSS SCD patients with priapism, with age ranging from 15 to 65 years. Laboratory diagnosis of SCD was done at the Sickle Cell Clinic of the Korle-Bu Teaching Hospital. Plasma nitric oxide metabolites were measured using Griess reagent system by ELISA method. Results: Mean NOx of 59.66±0.75 µMol/L in the comparison group was significantly different from those in steady state (P=0.02). During VOC, there was a significant reduction in mean NOx levels to 6.08±0.81 µMol/L (P<0.001). Mean NOx levels were however, significantly higher (50.97±1.68 µMol/L) (P<0.001) in the immediate postcrisis period. The mean NOx levels in the leg ulcer (21.70±1.18 µMol/L) (P<0.001) and priapism (28.97±1.27 µMol/L) (P<0.001) patients were significantly low as compared to the SCD patients in the steady state and comparison group. Conclusion: This study presents the first report on plasma NOx levels in SCD complication in Ghanaian SCD patients and confirms reduced plasma NOx levels in SCD patients in general. © 2018 Antwi-Boasiako and Campbell.
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    Arterial Stiffness Is Associated with Peripheral Sensory Neuropathy in Diabetes Patients in Ghana
    (Journal of Diabetes Research, 2018-01) Yeboah, K.; Agyekum, J.A.; Owusu Mensah, R.N.A.; Affrim, P.K.; Adu-Gyamfi, L.; Doughan, R.O.; Adjei, A.B.
    Objective Peripheral sensory neuropathy (PSN) is among microvascular complications of diabetes that make patients prone to ulceration and amputation. Arterial stiffness is a predictor of cardiovascular diseases and microvascular complications associated with diabetes. We investigated the association between PSN and arterial stiffness, measured as aortic pulse wave velocity (PWVao) and cardio-ankle vascular index (CAVI). Method In a case-control design, arterial stiffness was measured in 240 diabetes patients and 110 nondiabetic control. Large-fibre nerve function was assessed by vibration perception threshold (VPT) using a neurothesiometer. PSN was defined as the VPT > 97.5th percentile from age- and gender-adjusted models in nondiabetic controls. Results The overall prevalence of PSN was 16.6% in the entire study participants. Compared to non-PSN participants, PSN patients had higher levels of PWVao (9.5 ± 1.7 versus 8.7 ± 1.2 m/s, p = 0.016) and CAVI (8.4 ± 1.3 versus 7.6 ± 1.1, p = 0.001). In multiple regression models, VPT was associated with PWVao (β = 0.14, p = 0.025) and CAVI (β = 0.12, p = 0.04). PSN patients had increased odds of CAVI (OR = 1.51 (1.02–2.4), p = 0.043), but not PWVao (OR = 1.25 (0.91–1.71), p = 0.173). Conclusion PWVao and CAVI were associated with VPT and PSN in diabetes patients in Ghana. Patients having PSN have increased odds of CAVI, independent of other conventional risk factors.
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    Hematological parameters in Ghanaian sickle cell disease patients
    (Journal of Blood Medicine, 2018-10) Antwi-Boasiako, C.; Ekem, I.; Abdul-Rahman, M.; Sey, F.; Doku, A.; Dzudzor, B.; Dankwah, G.B.; Otu, K.H.; Ahenkorah, J.; Aryee, R.
    Background: Effective treatment and management of sickle cell disease (SCD) has been a challenge in Africa over the years. Hematological parameters are very useful profiles in the effective management of the disease. However, there is scarcity of studies on the hematological parameters of SCD in Ghana. This study aimed at determining hematological parameters among SCD patients with vaso-occlusion, those in the steady state as well as healthy controls at a teaching hospital in Ghana. Methodology: This was a cross-sectional study involving a total of 628 subjects, including 148 HbAA controls, 208 HbSS patients in steady state, 82 HbSC patients in steady state, 156 HbSS patients in vaso-occlusive crises (VOC), and 34 HbSC patients in VOC. Venous blood sample was collected from all study participants. A full blood count was done within 2 hours of collection, and hemoglobin (Hb) concentration, packed cell volume, red blood cell (RBC) concentration, mean corpuscular Hb, mean cell volume, mean corpuscular Hb concentration, and white blood cells (WBC) and platelet (PLT) counts were recorded. Results: WBC and PLT counts were significantly higher in both female and male patients with SCD, compared with their healthy counterparts (P<0.05). The level of WBC was, however, significantly higher in patients with HbSS VOC among the SCD patients (P<0.001). Levels of Hb, RBC, and hematocrit were significantly higher in the controls (P<0.001). There was no significant difference in mean cell Hb among male patients with SCD (P=0.274) and female patients with SCD (P=0.5410). Conclusion: The SCD patients had lower Hb and RBC than the controls; however, higher PLT and WBC are noted in various status of SCD, possibly reflecting spleen effect in these patients. Further studies are needed to confirm these findings.