PubMed Health⌕ Search

Biomedical subjects

G B Ogunmola

Publications and source records attributed to G B Ogunmola.

16 recordsLinked to original sources

Sickle cell anemia: a potential nutritional approach for a molecular disease.

A certain population of red blood cells in patients with sickle cell anemia has an elevated density and possesses an abnormal membrane. These "dense cells" have a tendency to adhere to neutrophils, platelets, and vascular endothelial cells, and, thus, they could trigger vasoocclusion and the subsequent painful crisis from which these patients suffer. We developed a laboratory method of preparing such dense cells and found that nutritional antioxidant supplements, hydroxyl radical scavengers, and iron-binding agents could inhibit the formation of dense cells in vitro. The concentrations at which effective nutritional supplements could inhibit dense cell formation by 50% were 4.0 mg/mL for aged garlic extract, 0.38 mg/mL for black tea extract, 0.13 mg/mL for green tea extract, 0.07 mg/mL for Pycnogenol, 930 microM for alpha-lipoic acid, 270 microM for vitamin E, 45 microM for coenzyme Q(10), and 32 microM for beta-carotene. Both an ex vivo study and a pilot clinical trial demonstrated that a cocktail consisting of daily doses of 6 g of aged garlic extract, 4-6 g of vitamin C, and 800 to 1200 IU of vitamin E may indeed be beneficial to the patients.

Adolescent↗

Haemolytic anaemia associated with Nigerian barbecued meat (red suya).

Five cases of haemolytic anaemia occurring in male Nigerians following the ingestion of spiced barbecued meat (suya) are described. Although suya is a popular food item in various parts of Nigeria, all five patients described in this report had consumed a special brand, called red suya, purchased from vendors at a popular road junction between the cities of Lagos and Ibadan. Ingestion of the culprit suya sample was followed within 24 h by malaise and fever, while passage of dark-coloured urine and jaundice followed 1-3 days thereafter. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was demonstrated by a fluorescent screening test in all cases, while the enzyme phenotype was shown to be GdA- in all four cases studied by starch-gel electrophoresis, thus suggesting that G6PD deficiency was a predisposing factor in the cases reported in this series. The haemolytic disease was self-limiting and full recovery followed in all cases. In view of the markedly circumscribed range from where the patients originated, the culprit agent responsible for the haemolytic disease is believed to be a recently introduced food additive that is probably accessible only to a limited number of suya vendors.

Adult↗

Polycythaemia rubra vera associated with unbalanced expression of the X chromosome and monoclonality of T lymphocytes.

Polycythaemia rubra vera (PRV) was diagnosed in a 69-year-old Nigerian woman whose haemolysate revealed an electrophoretically slow-moving homogeneous band of the enzyme glucose 6-phosphate dehydrogenase (G6PD). Further biochemical characterization identified the enzyme as a new sporadic G6PD variant. Electrophoresis of the haemolysate of 4 children of the proposita identified in a daughter a large quantity of the slow-moving variant enzyme, and a much lower quantity of the normal type enzyme, thus, signifying an extremely unbalanced mosaic phenotype situation. All other family subjects studied, including 2 sons, had the normal enzyme type B, thus confirming the heterozygosity of the proposita at the G6PD locus. Homogenates of platelets, granulocytes and E-rosette-forming lymphocytes of the proposita showed an identical slow-moving band as the haemolysate, thus, suggesting the origin of these cells from a common progenitor cell which may be either the pluripotent stem cell (PSC) or another precursor cell at an earlier level of development than the PSC. While the observation of preferential production of the variant enzyme may be attributed to the presence on the X chromosome of a 'haemopoietic gene', its relevance to the etiology of PRV is unclear.

Aged↗

Thyroid hormones and the reactivities of genetic variants of human erythrocytic glucose-6-phosphate dehydrogenase.

Thyroid hormones, throxine (T4) and triiodothyronine (T3) which are known to activate glucose-6-phosphate dehydrogenase (G6PD) activity in vivo act as substrate inhibitors of G6PD in vitro. T4 competitively inhibits NADP in human erythrocyte G6PD variants G6PDA, G6PDB and G6PDA- with inhibition constants of 2.40 +/- 0.90 X 10(-6), 3.44 +/- 0.63 X 10(-6) and 6.53 +/- 0.60 X 10(-6) mol/l, respectively. The inhibition is, however, noncompetitive with respect to G6P in the three variants. T3 also has similar inhibition pattern to T4 with inhibition constants for NADP of 1.9 +/- 0.08 X 10(-5) and 1.28 +/- 0.17 X 10(-5) mol/l for G6PDB and G6PDA-, respectively. cAMP on the other hand inhibits G6P competitively with inhibition constants 1.50 +/- 0.22 X 10(-4), 1.06 +/- 0.24 X 10(-4) and 1.76 +/- 0.14 X 10(-4) mol/l for G6PDB, G6PDA and G6PDA-, respectively. There are significant differences in the inhibition effects of T4 and cAMP with respect to NADP as substrates for the normal enzyme G6PDA or G6PDB and the deficient enzyme G6PDA- when NADP is the substrate, the latter being much more inhibited. The activation effect of thyroid hormones in vivo may therefore not be a direct result of thyroid hormone binding to the G6PD enzyme nor mediated through the action of cAMP but plausibly be through complexation of inhibitory trace metal ions by the thyroid hormones T4 and T3.

Cyclic AMP↗

PH dependent volume changes accompanying the binding reactions of human and pigeon methemoglobins.

Dilatometric measurements of the volume changes accompanying the binding reactions of azide ion to human adult and pigeon methemoglobins as a function pH at 25 degrees C demonstrate pH values of maximum volume change (pH delta Vmax) which are different for the different hemoglobins. pH delta Vmax occurs at pH 6.7 for human methemoglobin A and at pH 7.7 for pigeon methemoglobin. The pH delta Vmax occurs near the characteristic pH (pHch) of maximum enthalpy of the same binding reaction. It is shown that the large pH variation in delta V can arise if the configuration of charged groups on the surface of the molecule is different in methemoglobin and methemoglobin complex. When such a difference in configuration exists the addition of the same number of protons to methemoglobin and methemoglobin complex will give rise to different changes in the partial molar volume of the two species.

Animals↗

Hemoglobin chain recombination and the pattern of composition of hemoglobin S and D in heterozygotes.

The pattern of composition of hemoglobin in different heterozygotes for S and D hemoglobins is quantitatively accounted for by the relative rates of combination of the different chains alpha + beta A greater than alpha + beta D greatern than alpha + beta S greater than alpha + gamma. It is suggested that the recombination step may be one of the rate-limiting steps in hemoglobin assembly.

Adult↗

Isopycnic centrifugation of human, pigeon and guinea pig erythrocytes.

The buoyant densities of human erythrocytes with normal (HbAA) and abnormal heterozygous haemoglobins (HbSS, HbAS, HbSC) as well as erythrocytes from guinea pig and pigeon were determined by centrifugation in discontinuous density gradients of metrizamide. Guinea pig, pigeon and human erythrocytes from normal human adult (HbAA) and from heterozygote HbAS were found to have the same density of 1.1381 g/cm3, while erythrocytes from a sickle-cell patient (HbS) and from a heterozygote HbSC, HbSS and HbSC, which are known to have a higher lipid content than isovolumic normal cells, had a lower density of 1.1261 g/cm3. When centrifugation was carried out under non-equilibrium conditions (rate zonal), several sedimentation bands were obtained from each erythrocyte preparation. Differences in the sedimentation rates were unrelated to the haemoglobin composition of the erythrocytes. It is suggested that the lower density of the erythrocytes associated with sickle-cell disease may have significant consequences in the circulation of such cells and in the clinical sequence of the sickling process.

Anemia, Sickle Cell↗

The sensitivity of hemoglobin oxygen affinity to diphosphoglycerate and the characteristic pH of methemoglobin.

The sensitivity of the oxygen affinity of a hemoglobin to 2,3-diphosphoglyceric acid concentration has been defined as the change in log1/2O2 (deltalogp1/2O2) which results from saturating the hemoglobin with 2,3-diphosphoglyceric acid. The sensitivity varies from one hemoglobin species to another and is linearly rated to the difference in the logarithm of the binding constants of 2,3-diphosphoglyceric acid to deoxy- and oxyhemoglobin, the characteristic pH (pHch), and inversely proportional to the magnitude of the alkaline Bohr effect measured in a saturating amount of 2,3-diphosphoglyceric acid. Its magnitude is higher in large animals than in small animals and varies linearly with the charged amino acid composition of the hemoglobin. The charged amino acid residues must have been selected for in mammals with high metabolic needs and against in animals with low metabolic needs. Variability in the effect of 2,3-diphosphoglyceric acid on the oxygen transport in the different animal hemoglobins must therefore be the result of a positive Darwinian Selection of the charged amino acid residues in their hemoglobins. Furthermore, all the charged groups and not those at the binding site alone, affect the 2,3-diphosphoglyceric acid binding constant of a hemoglobin.

Animals↗

Effects of pressure on visible spectra of complexes of myoglobin, hemoglobin, cytochrome c, and horse radish peroxidase.

The spectra of the ferric form of most heme proteins [metmyoglobin, methemoglobin, horse radish peroxidase (EC 1.11.1.7), and ferricytochrome c at pH 1.5] are converted from high-spin (open crevice) structure to low-spin (closed crevice) form under pressure. Pressures up to 8000 kg/cm2 (780 MPa) have no effect on the spectra of high-spin ferro- and ferricytochrome c, which have a closed crevice structure at pH 7.0. Spectra of deoxy-ferromyoglobin and deoxy-ferrohemoglobin are reduced in intensity, but pressure does not change the positions of the absorption maxima. Cyanide ion prevents pressure-induced spectral changes in metmyoglobin and methemoglobin up to 8000 kg/cm2. Carbon monoxide (with a high affinity for the ferro heme iron) has a similar effect on ferromyoglobin and ferrohemoglobin. The pressure required to cause spectral changes in the heme proteins falls in the order, cytochrome c (pH 7.0) greater than horse radish peroxidase greater than myoglobin greater than hemoglobin. We have calculated a volume change of --50 cm3/mol associated with the configurational change accompanying the reformation of the iron-methionine bond in cytochrome c at low pH.

Cytochrome c Group↗

Volume changes in binding of ligands to methemoglobin and metmyoglobin.

The volume changes for the binding of various ligands to metmyoglobin and methemoglobin have been determined from the effect of pressure on the binding constants (for metmyoglobin) and by direct dilatometry (for methemoglobin). The volume changes associated with the binding of cyanide and azide ions to methemoglobin are pH-dependent. The volume change for the binding reaction is evidently affected by the same subtle structural variations that have been judged to be present from the variation with pH of enthalpy and entropy for the binding reactions in these proteins. Hydration changes and spin state changes which have been postulated to be linked with structural variations in these proteins must be pH-dependent.

Atmospheric Pressure↗

Green tea extract and aged garlic extract inhibit anion transport and sickle cell dehydration in vitro.

Both green tea extract (GTE or tea polyphenols) and aged garlic extract (AGE) effectively inhibited in vitro dehydration of sickle red blood cells induced by K-Cl cotransport or red cell storage. For K-Cl cotransport induced by 500 mM urea, 0.3 mg/ml EGCg (epigallocatechin gallate; a major component in GTE) almost completely inhibited dehydration, and 6 mg/ml AGE inhibited dehydration to 30% of the control level. Both vitamins E and C had no effect at the level of 2 mM. Different tea extracts had different degrees of inhibition, but the inhibitory activity increased when the number of hydroxyl groups in the compounds increased. With storage of sickle cells at 4 degrees C for 6 days, the cells started to undergo spontaneous dehydration when incubated at 37 degrees C. Neither inhibitors for Ca-induced K efflux nor K-Cl cotransport could inhibit cell dehydration of stored sickle cells, but both GTE and AGE effectively inhibited it. Chloride efflux measurements using a chloride electrode demonstrated that both GTE and AGE inhibited anion transport in red blood cells. The inhibitory mechanism of these compounds may be related to anion transport inhibition, although involvement of their antioxidant activities can not yet be ruled out.

Anemia, Sickle Cell↗

Haemoglobin DIbadan in a haemoglobin S endemic population.

Haemoglobin DIbadan (beta 87 threonine leads to lysine) was originally found in Ibadan, an area with a high incidence of sickle cell haemoglobin (HbS). Since haemoglobin D and S are indistinguishable by most common conventional methods, the geographical coincidence of the two haemoglobin poses a serious screening problem which was investigated in the propositus who is heterozygous for S and D, his wife who is heterozygous for A and S, and their six children. The combined techniques of haemoglobin solubility, sickling rate, shaking test and routine electrophoresis have yielded an unequivocal diagnosis of the haemoglobin types of the family both for identification and quantitative estimation of the percentage of haemoglobins in the heterozygotes. HbD was found to be slightly less soluble than HbA but otherwise normal blood from S+D individuals was found to contain 57-60% HbD suggesting an increased systhesis of HbD relative to S, whereas A+D heterozygote has 41% HbD suggesting a diminished synthesis of HbD relative to HbA. The physicochemical characteristic of HbD and the haematological data in simple heterozygotes are normal.

Adolescent↗