FACULTY OF BASIC MEDICAL SCIENCES

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IMMUNOPATHOLOGY OF AMOEBIASIS IN IBADAN
(1971) ABIOYE, A. A.
Amoebiasis exemplifies a disease of protean manifestations which presents many perplexing problems. In this thesis an attempt is made to define a number of the wide variations which have been observed in the pathological manifestations of the disease. The work consists of both retrospective and prospective Studies. The retrospective study involved a review of the 7922 protocols of the autopsies at the University College Hospital, Ibadan, during the ten year period 1958 to 1967. 135 cases in which lesions of amoebiasis were described, were selected for special study using 276 cases of other diarrhoeal diseases as controls. The results of this review defined the pathology and complications of amoebiasis seen at the UCH, during the period covered by this study. A prospective study which included field surveys. laboratory studies on patients and controls; and in-vitro studies of the parasite was also carried out. Parasitological, biochemical and immunological techniques were applied in the prospective study of 1291 subjects in a field survey. In addition some 200 hospital materials were included in the prospective study. The results obtained provided the basis for the suggestions made concerning the different methods that can be applied to the future study of the prevalence of amoebiasis in any given population exposed to the risk of infection by Entamoeba histolytica. Local (Ibadan) strains of Entamoeba histolytica have been successfully cultured and the in-vitro characteristics studied. From the materials provi.ded by the in-vitro cultures of the organism, investigations have been made on E. histolytica antigens and the corresponding antibodies produced in man. The results of these investigations have been utilized in immunological studies, designed to define the mechanism of production of some of the problems posed by amoebic infections. The severity and high fatality of the disease in pregnancy and puerperium, was studied in detail. The observation that amoebiasis tends to be more severe and to have a higher mortality in pregnant and puerperal women was made only recently. At the time the present studies were planned, the association of pregnancy with severe amoebiasis had not been well established, and the mechanism for this association was unknown. It was, however, wall known that pregnant women were more liable to severe for-ms of certain other infectious diseases and it was considered possible that a similar mechanism might be operating in the case of amoebiasis. The present work confirms these clinical observations. Thus from the statistical analyses of the results of both the autopsy and prevalence studies, it became evident that the high fatality of amoebiasis during pregnancy and the early puerperium was not fortuitous but real. A fulminating type of lesion affecting the whole length of the large bowel is commoner in pregnant women and in those in the early puerperium dying of amoebiasis, than in any other cases of amoebiasis seen at autopsy. Furthermore, the biochemical and immunological studies help to throw some light on the mechanism of the selectivity of Infection by E. histolytical. These same results, also provide some explanation for the severity of amoebiasis during pregnancy and the allied states. The conclusions, support the hypothesis of lowered resistance to infectious diseases during pregnancy. Speculative submissions are, therefore, made on the defective immune mechanism occurring during pregnancy and the early puerperium. Thus, the inability of pregnant women to produce 'sufficient antibodies' to amoebic infections, demonstrated by the reactivity of the immunoglobulins in amoebiasis, confirms the suspicion of the existence of a derangement of host-defence mechanisms during pregnancy. This raises the hope and encourages future search for the specific serum agents) which may account for the deranged immune mechanism. On similar basis, the characterization of amoebic antigens together with that of the corresponding antibodies, offers a new field in the study of the immunopathology of amoebiasis. In conclusion, from the combined autopsy, prevalence, in-vitro experimental, biochemical, and immunological studies, it is submitted: 1. That the association of pregnancy with the severe form of amoebiasis at least, in this part of the world, is one of the perplexing problems posed by the disease. 2. That chronic amoebic infection is associated with the development of growth-inhibiting factors in the serum, for example, in patients with amoebic liver abscess. 3. That, on the contrary, growth promoting factors were demonstrated in the sera of pregnant/puerperal women with or without acute amoebic dysentery. 4. It is suggested that the severity of the disease in pregnant/puerperal women is a reflection of the derangement of immune response during pregnancy, with particular reference to the production of serum immunoglobulins.
A STUDY OF THE INTERACTIONS BETWEEN PLASMA CORTISOL LEVELS, ESTROUS CYCLES, RECTAL TEMPERATURES AND RESPIRATORY RATES IN HEIFERS
(1978-06) ADEYEMO, O.
The need to improve the animal protein diet of the Nigerian population has underlined the importation of temperate-evolved cattle into Nigeria. How these animals adapt to the new environment should be of economic and scientific interest. Under the natural hot/humid subequatorial climate of Ibadan, some physiologic, adrenocortical and reproductive functions were investigated in 6 German Brown, 5 Holstein and 6 White Fulani heifers. The Brown/ Holstein and Fulani heifers attained puberty at the average eyes, with the standard deviation, of 17.8 + 1.6, 16.7 + 1.8 and 23.7 + 1.9 months respectively. Observations on estrous cycles showed that estrous period ranged between 7 and 31 hours in the three breeds, the mean values, with the standard errors, being 16.2+0.7, 15.8 ± 0.7 and 14.6 +_0.8 hours in the Brown, Holstein and Fulani heifers respectively. The difference between the Bos taurus and Bos indices cattle was slight but significant. Most estrus commenced during the day with a greater concentration in the morning time. The intensity of estrus was high in both species though, occasionally, a few Fulani heifers showed weaker estrual signs. Average estrous cycle length was slightly longer in the Brown and Fulani than in the Holstein heifers, the values, with the standard errors, being 21.0 + 0.3, 21.4 ± 0.2 and 20.1 + 0.2 days respectively. Ovulations occurred mostly within a day after estrus, and this as well as the duration of estrus and estrous cycle length showed no seasonal variations. There was no indication that Bos taurus and Bos indicus cattle under the semi-intensive management preferred any particular season for increased sexual activity or breeding in the sub-equatorial climate. Marked shifts occurred in the respiratory rates during four selected quarters of the year. Increases occurring in the dry hot season from the values in the relatively cooler season were highly significant. Both mean morning and mean afternoon values (l4 - 44 and 17 – 75 breaths per minute respectively) were highest in the Holstein and lowest in the Fulani heifers. Rectal temperatures showed slight but significant seasonal changes. Mean values were 101.3°F (38.5°C) and 102.2°F (39.0°C) in the morning and afternoon respectively for all the heifers together through the year. The lowest afternoon values occurred in the wettest and coolest months. The Fulani and Holstein heifers showed the lowest and highest mean values respectively. Diurnal and circadian shifts in the respiratory rates and rectal temperatures in the heifers were most exaggerated in the sun and in the Holsteins, the latter particularly exhibited polypnea and hyperthermia. Unlike the zebu, the Bos taurus cattle sought shade in the sun. The Holstein heifers sought shade more frequently and stayed there longer than the Brown heifers. Basal plasma cortisol concentrations at 07 - 08.00 hours, determined by radioimmunoassay during four quarters of the year was low, ranging between 1 - 10 ng/ml with occasional mid-cycle and more frequent- . proestrual and/or estrual elevations. Mean values showed slight but significant seasonal changes. The levels in the dry season were slightly lower than in the wet season. Breed differences were not significant. Diurnal and circadian plasma cortisol concentrations in heifers in the shade and in the sun showed no rhythmical pattern. Exogenous corticotrophin at and after mid-cycle stage elicited marked and prolonged adrenocortical response which varied between heifers, and did not alter estrous. cycle rhythmicity. A high adrenal reserve in the heifers was indicated. Bos taurus cattle have been found to be adaptable to the southern Nigerian climate represented by the Ibadan condition. Management practice should, however, ensure all-year-round provision of shade and adequate nutrition including the adoption of night grazing. The Brown cattle are recommended over the Holsteins because the former are more comfortable, A mixed herd of the two breeds should be discouraged because socially the Browns dominate over the Holsteins. The Fulani cattle are more adaptable to the subequatorial climate than the temperate-evolved cattle as evidenced by the physiological responses, artificial breeding should be suitable for the Fulani cattle as it is for the Bos taurus cattle. The need to adopt better management practices than hitherto existing, range system for the Fulani cattle so that their reproductive and productive attributes may be well manifested, is indicated.
CATION CONTENT AND FLUXES IN RED CELLS OF NORMAL AND HYPERTENSIVE NIGERIANS
(1978-08) ADEROUNMU, A. F.
RED CELL SODIUM AND POTASSIUM CONTENT AND FLUXES IN NORMAL AND HYPERTENSIVE NIGERIANS. 1. Erythrocyte sodium, potassium and water content have been determined in 908 Nigerians so as to: 1. establish normal values in Nigerians 2. compare values in Nigerians with known values in other blacks. 3. compare values in Nigerians with those of caucasians. Red cell sodiuum, potassium and water were also determined in 7 caucasians who had been resident in Nigeria for periods varying from 6 months to 18 years. The RBC sodium for Nigerians considerably higher than those of caucasians, but the RBC potassium and water did not show any significant difference. In the course of this work, the normal (control) subjects were grouped according to their genotypes. 3 genotypes were encountered: AA, AS and AC. There was no significant difference in the erythrocyte sodium, potassium and water of the individuals belonging to these 3 genotypes. The results were also analysed for sex and age differences, and none was found. Results of erythrocyte sodium, potassium and water from 3 siblings and their mother were also presented. These results differed, from one another, suggesting that environmental factors are also important and probably just as potent determinants of RBC sodium, potassium and water content as are genetic factors. 2. 100 hypertensive subjects were studied. They were all newly diagnosed, mostly symptomless ambulant subjects who were attending the medical out-patient department of the University College Hospital, Ibadan. Their main pathological finding systemic hypertension. They were followed up for periods varying from 18 months to 3 1/2 years. Investigations were performed on each patient which enabled their being grouped into hypertensives with normal renal function or hypertensives with abnormal renal function. Only those with normal renal function were included in the study. The results obtained for the red cell sodium and potassium were significantly different from those of the Controls. Their red cell water was also significantly different from that of the Controls, but the difference m RBC water was not sufficient to account for the differences in the RBC sodium and potassium. Here again, the RBC sodium and potassium were not related to age or sex. The RBC sodium and potassium content were in no way related to the mean blood pressures. Their values remained the same both before and during treatment. Adequate control and maintenance of the patients blood pressures within the normal range did not affect these two cations. 3. When red cells from Controls and red cells from Hypertensives were exposed to a high sodium load, the RBCs from hypertensive gained a lot more sodium and lost a lot more potassium than the RBCs from Controls. 4. Normal red cells lost their potassium into isotonic sucrose media seven times as fast as red cells from hypertensive subjects. 5. Normal red cells have a slightly higher a tive sodium flux per hour than red cells from hypertensive subjects, but the difference is not statistically significant. The rate constant for active sodium flux is higher for red cells of Controls than for red cells of hypertensive subjects, but the correlation between intracellular sodium content and rate constant is not good (r= -0.43). The rate constant for the red cells of the hypertensives is lower, but it correlates better with the red cell sodium (r =0.53).
INTERACTION OF PROSTAGLANDIN E(2) (PGE(2)) WITH NORADRENALINE AND ITS ANTAGONISTS IN THE ISOLATED MESENTERIC ARTERY OF RAT
(1980-07) ADEAGBO, A. S. O.
The effect of PGE(2), PGF(2a) and PGI(2) on constriction induced by different mechanisms was studied in the isolated rat mesenteric artery as described by McGregor (1965) Vasoconstriction was induced by mechanisms involving dif modes of calcium utilization viz: (i) Pharmacomechanical pathway by low doses of the adrenergic neurotransmitter, noradrenaline acting at α- receptor; (ii) electromechanical pathway by high potassium and (iii) agents which facilitate Ca(2t) influx e.g. A23187. The prostaglandins potentiated the vasoconstrictor effect of NA. Potentiation factors calculated from different doses of the prostaglandins showed the effects of the prostaglandins to be dose - dependent and PGE(2) to be significantly more potent (P>0.005) than PGF(2a) and PGI(2). The prostaglandins failed to potentiate high potassium - induced vasoconstriction. PGE(2) also failed to potentiate NA if the vasoconstrictor effects were evoked in Ca(2+) - free Krebs solution; but the degree of potentiation increased with increase in the concentration of Ca(2+) ions in the perfusion fluid. This result suggested strongly that the potentiation was associated with external calcium. Evidence is presented to show that potentiation was not prejunctional since cocaine, bretylium and reserpine pretreatment did not materially alter the effect of PGE(2). It was concluded that prostaglandins potentiated NA vasoconstriction by facilitating Ca(2a) influx. The mechanism of this facilitation is discussed. NA vasoconstriction was competitively antagonised by adrenoceptor antagonists-phentolamine, tolazoline, yohimbine and phenoxybenzamine (in low concentrations). The blockade caused by these antagonists was reversed by PGE(2). By comparing NA dose-ratios in the presence of antagonist with dose-ratios in the presence of antagonists plus different doses of PGB(2), I showed 1hat the degree of reversal was related to the dose of PGE. For example, the NA dose - ratio for yohimbine (1.28 x 10(-6)M) was reduced from 26.6 + 0.9 to 1.7 + 0.1 when PGE(2) (2.8 x 10(-8) M)was included in the perfusion fluid with the antagonist. The reverse of antagonism was not due to a change in the binding characteristics of the α- adrenoceptor since pA(2) values for the antagonist were not significantly different (P<0.05) when PGS was included with the antagonists. Evidence is presented which suggests that reversal of antagonism involved utilization of internally bound calcium since reversal of antagonism occured even after the omission of Ca(2+) from the external medium. In this sense, the mechanism of reversal was different from that of potentiation. Furthermore, the degree of reversal (measured as-reversal factor) was quantitatively greater than would be the case if reversal was simply a reflection of the enhgresponsiveness of the vascular muscle to NA. In contrast to the "competitive” α- adrenoceptor antagonists, PGE(2) did not reverse the block of NA vasoconstriction caused by phenoxybenzamine (high doses); verapamil, cinnarizine or prazosin. All these agents caused blockade of NA that was not competitive in nature. Since none of the competitive α- adrenoceptor antagonists prevent prostaglandin formation; the point is made, that a prostaglandin can reverse NA blockade even if the blockade did not involve inhibition of prostaglandin synthesis.
POST-JUNCTIONAL ALPHA ADRENOCEPTORS IN THE ANOCOCCYGEUS MUSCLE AND VAS DEFERENS: A COMPARATIVE STUDY IN NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
(1984-06) ADENEKAN, O. O.
The characteristics of the post-junctional α-adrenoceptors in the isolated anococcygeus muscle and vas deferens were compared in spontaneously hypertensive rats (SHR) and normotensive rats (NCR). Responses to α —adrenoceptor agonists were obtained in the absence and presence of cocaine and of antagonists. Noradrenaline (NA) and phenylephrine (PE) produced concentration related contrations of the preparations which were antagonised by phentolamine, prazosin and yohimbine in both rat strains, indicating α -adrenoceptor mediation. The effects of cocaine revealed the relative efficiency of the uptake mechanism in each preparation. In the anococcygeus NA was equipotent in the NCR and SHR in the absence of cocaine whereas it was less potent in the SHR in the presence of cocaine, PE was less potent in the SHR in the absence and presence of cocaine. Antagonism was assessed by pA2 and K(diss) determinations. Potencies were compared only when antagonism was competitive in both strains. In the anococcygeus low concentrations of prazosin (L-Praz) non—competitively antagonised NA but antagonised PE equally and competitively in both strains. Higher concentrations (H-Praz) competitively antagonised NA in both strains. Phentolamine was competitive against NA in NCR and against PE in both strains. However, it was non-competitive against NA in SHR, Low concentrations of yohimbine (L—YOH) competitively antagonised NA and PE in both the NCR and SHR but the K(diss) values were significantly different. Higher concentrations (H—YOH) was competitive against NA in the NCR and PE in both strains. In the vas L-Praz competitively antagonised both NA and PE in the NCR but gave non—competitive antagonism of both strains in the SHR, Phentolamine antagonised NA competitively in the NCR but non-competitively in the SHR. It was equipotent and competitive against PE in both strains. L—YOH non-competitively antagonised NA and PE in the NCR but in the SHR it was competitive. H-YOH antagonism was non—competitive against both NA and PE in both strains. It is suggested that there might be both the α1— and α2 post—junctional adrenoceptor in the NCR anococcygeus muscle, Prazosin and yohimbine seem to be able to differentiate between the two receptor subtypes at low concentrations, It is suggested further that the α2- subpopulation might not possess identical characteristics in the NCR and SHR anococcygeus. Also, there might be an alteration in NA uptake properties in the SHR, In the NCR vas deferens there seems to be a predominance of post-junctional α1-adrenoceptors. In the SHR vas, there might be an increase in the post-junctional α-adrenoceptor population and/or sensitivity. Furthermore, it seems that the post—junctional α2-adrenoceptor characteristics are somewhat different in the SHR, Uptake1 is suggested to be less efficient in the SHR vas.
Dietary salt and the glycaemic response to meals of different fibre content
(The Macmillan Press Ltd., 1989) Akanji, A. O.; Charles-Davies, M. A.; Ezenwaka, C.; Abbiyesuku, F. A.; Osotimehin, B. O.
In attempting to resolve the existing controversy on the effect of dietary salt intake on glycaemic responses, wc investigated post-prandial plasma glucose levels in 10 healthy normal weight non-diabetic Nigerian subjects (aged 23.1 years ± 1.3 (s.e.m.) with body mass index, BMI 19.9 ± 0.6kg/m2) consuming equal amounts of carbohydrate from glucose, boiled yam (tow fibre content of 0.9 per cent raw tuber weight) and boiled black-eyed peas (high fibre content of 4.8 per cent dry weight) with and without added table salt (4.25g). The results indicated no significant differences in fasting, peak and 2-h plasma glucose concentrations and total and incremental areas under the 3-h glucose/time curves in the subjects consuming each meal with and without added salt. Added salt had no influence on the glycaemic index of each meal. We conclude that salt has no effect on the glycaemic response to plain glucose or meals with varying fibre content even in a population known to demonstrate defects in salt handling.
Plasma glucose and thiocyanate response to different mixed cassava meals in non-diabetic Nigerians
(The Macmillan Press Ltd., 1990-01) Akanji, A. O.; Adeyefa, I.; Charles-Davies, M.; Osotimehin, B. O.
We measured plasma glucose and thiocyanate levels before and up to 4 h after feeding 11 overnight fasted healthy non-diabetic volunteers randomly on three occasions each with three locally consumed cassava meals: (i) gari as eba 50 g; (ii) lafun 50 g and (iii) parboiled cassava flakes 76 g. Each of these meals contained 175 kcal (0.7 MJ) and was consumed with a sauce to a total caloric value of 300 kcal (1.26 MJ). On the fourth visit, each volunteer consumed 75 g glucose. While the peak and 2-h glucose values were greatest with oral glucose (P less than 0.01), they were similar with the three cassava meals, although tended to be lowest with lafirn. Similarly, areas (incremental and total) under the glucose/time curves were highest with oral glucose (P less than 0.05), but while eba and cassava flakes were similar, lafun had the lowest values (P less than 0.05). Plasma thiocyanate levels were unchanged after ingestion of oral glucose and eba, but increased to peak values (P less than 0.05) by 14 per cent on cassava flakes and by 23 per cent on lafun. We conclude that post-prandial glycaemia and plasma thiocyanate levels after cassava meals depend on the mode of preparation of the meal and that lafun showed the least glycaemic response of the three cassava meals tested although it caused the greatest increase in plasma thiocyanate levels. These findings suggest that a cyanogenetic potential does not always reflect a tendency to hyperglycaemia.
SOME CONSEQUENCES OF THE BINDING OF AFLATOXIN B1 WITH PLASMA MEMBRANE ON THE REGULATION OF INTRACELLULAR Ca2+ HOMEOSTASIS
(1992-03) ADEBAYO, A. O.
The possible influence of aflatoxin B1 a potent hepatocellular carcinogen on the regulation of intracellular Ca2+ homeostasis has been studied using the red cell as a model. Preliminary work on the interaction of the toxin with the red cell membrane using spectrofluometric analysis indicated that the toxin binds spontaneously and irreversibly to the red cell membrane. The binding is highest at pH 4 and least at pH 10. Results obtained from studies using equilibrum dialysis technique show that about 4 nmoles of the toxin bind to one microgram membrane protein. Although the exact membrane component to which aflatoxin B1 binds is not known, experiments carried out to determine the influence of aflatoxin B1 on the activity of the calcium pumping protein revealed that the toxin inhibited the calmodulin-stimulated erythrocyte membrane Ca2+ -ATPase activity by about 50 percent, while it has little or no effect on its basal activity. Kinetic analysis of the inhibition shows that, the toxin reduces the Vmax and Km of the calmodulin-stimulated enzyme by 50 percent in a non-competitive manner, On the other hand, the carcinogen had no significant influence on the kinetic parameters of the enzyme in the non-activated state. Similar results were obtained for the triton X-100 solubilized and calmodulin affinity chromatographed enzyme. In this instance aflatoxin B1 inhibited the calmodulin-stimulated purified enzyme by 50 percent with or without preincubation on ice for half an hour. Again, the toxin had little or no effect on the basal activity of the enzyme in the absence of calmodulin. Analysis of the results obtained using varying concentrations of ATP shows that the Km and Vmax of the non-activated enzyme were not altered by the toxin while both the Vmax and Km values were reduced by about 50 percent in the presence of calmodulin. In addition aflatoxin B1 inhibited Diphosphotidyl glycerol (cardiolipin) by about 28% while it has no effect on the basal activity of the enzyme. Although, the inhibition of the membrane bound or purified Ca2+ ATPase by the toxin is concentration dependent, varying concentrations of phosphatidyl serine and phosphatidyl choline do not affect the inhibition of the purified enzyme by afla toxin B1. Results obtained with triton X-100 solubilized enzyme shows that triton X-100 alone could not activate the enzyme. Thus at triton X-100: protein ratio of 2, the enzyme was stimulated by calmodulin. This activity was sensitive to inhibition by the toxin. In this instance, the calmodulin-stimulated activity was inhibited by about 50%, while at lower ratios of the triton X-100 to protein there was no significant inhibition of enzyme. Results of experiments carried out on the 124KDa fragment, which was produced as a result of exposure to calpain a Ca2+ - dependent cysteine protease, indicated that the toxin has no effect whatsoever on the activity of the fragmented enzyme, Similarly experiments on limited proteolysis of the Ca2+ ATPase by trypsin to give the 90KDa fragment which still retains its calmodulin binding domain and the 76KDa fragment which has lost its calmodulin binding domain revealed that the aflatoxin inhibited the 90KDa fragment by about 50% while the 76KDa fragment is not affected at all. Altogether, -these findings show that aflatoxin B1 inhibits the plasma membrane Ca2+ - pumping ATPase by interacting with the enzyme at the calmodulin binding domain. The nature of the exact amino acid residue to which the toxin binds is however not known. The implication of these observations is that Ca2+ extrusion may be hampered in situations where the cell is poisoned by the aflatoxin
THE MODULATION OF RAT LIVER MICROSOMAL CALCIUM ION-PUMPING ATPase BY DICOPHANE AND LOW PROTEIN INTAKE
(1992-05) ADENUGA, G. A.
The effects of the liver tumour promoter, dicophane, with those of low protein intake (LPI) on the functional expression of rat liver microsomal Ca(2+) -ATPase were compared. The effects of dicophane and LPI on the activity of the microsomal enzyme after carcinogenic initiation by pretreatment with aflatoxin B (AFB), a genotoxic liver carcinogen, were also compared. The Status of membrane - bound Ca(2+) -ATPase of erythrocytes of humans having primary liver cancer (PLC) and kwashiorkor was assessed. The specific activity of membrane - bound microsomal Ca(2+) -AT Pase of the livers of untreated rats was 4.543 ± 0.857 µmole P/mg protein/hr. at pH 8.0 and was insensitive to calmodulin. The specific activity of the enzyme was significantly decreased (P < 0.01) following subcutaneous administration of a single dose of 75mg dicophane/kg body wt.; the affinity of the enzyme for Ca(2+) was however unaffected. Similarly, liver microsomal Ca (2+)-ATPase activity was significantly diminished following the ingestion of low protein diet by rats for 12 weeks. The mean Ca(2+) -ATPase activity of AFB -treated animals (in the absence of dicophane) was not significantly different (P > 0.05) from that of AFB-treated rats which subsequently received dicophane. In contrast, liver microsomal Ca(2+)-ATPase activity of animals fed low protein diet prior to and after AFB ingestion was higher (P < 0.05) than that of animals which were on low protein diet only. Basal activity of erythrocyte Ca(2+) -ATPase in paediatric controls and those having kwashiorkor (protein-energy-malnutrition) were similar (P > 0.05); similar observations were made between normal adults and those suffering from PLC. Erythrocyte Ca(2+) -ATPase of either PLC or kwashiorkor patients was however, some- what, less sensitive (15-40 %) to the stimulatory effect of calmodulin, an endogenous activator of the Ca(2+) -pump. These results suggest that liver microsomal Ca(2+) -ATPase could be a useful biochemical marker to determine the onset or occurrence of tumour promotion in liver cells. Finally, chronic dietary protein malnutrition mimics the effect of chemical liver tumour promoters and could possibly enhance the development of human PLC particularly n those areas of the tropics where malnutrition is prevalent. Future confirmatory experiments are however re-quired to fully justify this postulate.
MALARIA PARASITAEMIA AND HUMORAL IMMUNE RESPONSES TO SOME DEFINED PLASMODIUM FALCIPARUM ANTIGENS IN NEWBORNS, INFANTS AND ADULT NIGERIANS
(1994-08) ACHIDI, E. A.
A cohort of mothers and then newborns at Igbo-Ora, Oyo State was studied longitudinally for 12 months to determine the incidence of malaria parasitaemia, episodes of clinical malaria and their humoral immune response to malaria infection. Cross-sectional studies were also performed on adults at the Government Technical College, Igbo-Ora and blood donors at the University College Hospital, Ibadan during the rainy and dry seasons. Peripheral and cord blood samples were collected from 116 women at delivery and maternal-newborn malariometric indices were recorded. Infants were monitored fortnightly to detect episodes of clinical malaria and serial blood samples were collected at bi-monthly clinics. Blood samples were collected from 100 volunteers at the G.T.C. Igbo-Ora in July, 1991 and 33 of these volunteers in February, 1992; 224 blood donors at the U.C.H., Ibadan between October and November, 1991 and in 192 donors in March, 1992. Immunological assays included single radial immunodiffusion assay for IgG, IgM and IgA; immunofluorescence assay for antibodies to total blood stage antigens; erythrocyte membrane immunofluorescence (EMIF) assay to detect antibodies to the Pfl55/RESA; and an enzyme-linked immunosorbent assay (ELISA) for antibodies to four synthetic peptides. Malaria parasites were detected in 2.5% of cord blood samples and in 22.4% of the parturient women. The malaria parasite rates and densities of the study infants increased significantly with increasing age. Parasite rates at the July and February surveys at the G.T.C. were similar (P>0.50) while parasite density was higher (P<0.01) at the July survey. The parasite rate of blood donors at the October-November survey was higher (P<0.001) than at the March survey while parasite density in March was higher (P<0.001) than at the October-November survey. Cord blood IgG was significantly lower than maternal IgG levels and a correlation was observed between cord and maternal IgG but not IgM levels. During the first year of life, IgM but not IgG and IgA was significantly higher in malaria positive infants compared with negative infants. Antibodies to total blood stage antigens were detected in all sera tested. Malaria-specific IgM was detected in 5.8% of cord blood samples. There was a correlation between maternal and cord blood antibody titres to the Pfl55/RESA (P<0.001) antigen. In addition a correlation was obtained between maternal and cord blood ELISA (OD405) values to the (EENV)6, LJ5 and MAP2 peptides but not (NANP)6 peptide. There was no correlation between cord blood IgG, IgM, anti- Pfl55 antibody titres, ELISA (OD405) values to the (EENV)6, (NANP)6, U5 and MAP2 peptides and duration of onset of malaria in the infant. Cord blood seropositivity for antibodies to the Pfl55/RESA and (NANP)6 antigens or (EENV)6 and (NANP)6 peptides did not influence age of onset of clinical malaria. However, infants with haemoglobin AS whose cord blood was seropositive for antibodies to the Pfl55/RESA and (NANP)6 antigens or (EENV)6 and (NANP)6 peptides showed delayed onset of clinical malaria compared with AA infants. In adults, anti-Pfl55 antibody titres and ELISA seroreactivities to the (EENV)6, LJ5 and MAP2 peptides showed a wide variation and individual levels were similar on consecutive surveys. Seroreactivity to the (NANP)6, was higher at the end of the rainy season than at the end of the dry season. The presence and level of antibodies to the Pfl55/RESA, (EENV)6, (NANP)6, U5 and MAP2 antigens did not influence the presence and density of malaria parasites. Parasitological data in infants suggest some relative protection within the first 2-3 months of life. However, maternally acquired antibodies alone may not be responsible for this observation. The presence of malaria-specific IgM in cord blood suggest intrauterine sensitization of the foetus by malarial antigens. Although no relationship was observed between malarial antibody levels and parasite rates/densities in the adult subjects, these antibodies may still play a role in immune protection against malaria.
Hepatitis B and C virus and hepatocellular carcinoma
(1997) Olubuyide, I. O.; Aliyu, B.; Olaleye, O. A.; Ola, S. O.; Olawuyi, F.; Malabu, U. H.; Odemuyiwa, S. O.; Odaibo, G. N.; Cook, G. C.
"Antibody to hepatitis C virus (anti-HCV) was detected in 18.7% of patients with hepatocellular carcinoma ma (HCC)a nd in 10.9% of controls (P<0.001).The corresponding prevalences of hepatitis B surface antigen [HBsAg] were 59.3% and 50.0%(P<0.001). Using paticnts with non-hepatic disease as controls stepwise logistics regression analysis indicated that both anti-HCV (odds ratio 6-88%; 9.5% confidence interval [CI] 1.63-9-77) and HBsAg (odds ratio 6.46; 95% Cl 1.68-18:13) were independent risk factors for HCC. Calculation of the incremental odds ratio indicated no interaction between hepatitis B virus {HBV) and HCV. Blood transfusion was a significant risk factor for acquiring HCV infection with odds ratios of 5.48 (95% CI 1.07-29.0) and 2.86 (95%. CI 1.31-22.72) for HCC cases and controls, respectively. The mean age HCC cases with HBsAg and anti-HCV was lower than that of HCC patients with anti-HCV alone (p<0.01). It is concluded that there is a high rate of HBV infection, and a low rate of HCV infection, among Nigerian patients with HCC. However, HBV and HCV are independent risk factors for the developement of HCC, with HBV having an effect more rapidly. Screening of blood products for transfusion might minimize the risk of HCV transmission."
Hepatitis B and C in doctors and dentists in Nigeria
(Oxford University Press, 1997) Olubuyide, I. O.; Ola, S. O.; Aliyu, B.; Dosumu, O. O.; Arotiba, J. T; Olaleye, O. A.; Odaibo, G. N.; Odemuyiwa, S. O.; Olawuyi, F.
"We surveyed a random sample (n=75) of doctors and dentists at University College Hospital, Ibadan, Nigeria. They were offered anonymous testing for hepatitis B surface antigen (HBsAg), hepatitis B antibodies to hepatitis B core antigen (anti-HBc) and to hepatitis C virus (anti-HCV) by enzyme immunoassay. The results suggest a high prevelance of hepatitis B virus (HBV) with a high potential of transmissibility, as well as a high prevalence of HCV infection. The majority of the doctors and dentist use universal precaution for protection against viral hepatitis on <50% of the occasion when they carry out procedures on their patients. Infection with HBV was associated with type of specialty (surgeaon, dentists) and lack of HBV vaccination (p<0.05). After logistic regression, these factors, were independently associated. with HBV infection (p<0.05). Sixty (80%) had not hepatitis received prior HBV vaccination. Unvaccinated personnel were more likely to be surgeons, dentists, <37 years of age, and have fewer years of professional activity (p<0.05). After logistic regression, only fewer years of professional activity remained independently associated with lack of vaccination (p<0.05). To reduce the occupational exposure of doctors and dentists use universal precaution must be rigorously adhered to when the doctors and dentists carry out procedures on their procedures on their patients, and all health-care workers should be vaccinated with HBV vaccine and the HCV vaccine, when it becomes available."
Human immunodeficiency virus types 1 and 2 infection in some rural areas of Nigeria
(1998) Odaibo, G. N.; Olaleye, O. D.; Tomori, O.
The prevelence of human immunodeficiency virus types 1 and 2 in rural areas of Nigeria was estimated using 1089 sera collected in 18 locations from 1992 to early 1994. The sera were tested with Enzyme Linked Immunosorbent Assay(ELISA) and confirmed by western immunoblotting technique. Overall, 13 (1.2%) of the 1089 sera were positive for antibodies to HIV-1 and HIV-2. Prevalence of 0.6% and 0.8% were obtained for HIV-1 and HIV-2 (50.0%) were found in Zurhlrrua and Umubuzu. A seroprevalence of 1.2% was obtained for both male and female groups tested. The highest prevalence of HIV was found among individuals 30-39 years age group. An overall increase in prevalence of HIV-1 and HIV-2 infection was obtained over the three years during which samples were collected for this study (0.7% in 1992, 1.0% in 1992 and 3.4% in 1994). In addition, two sera were positive for both HIV-1 and HIV-2. The detection of antibodies to HIV-1 and HIV-2 in the rural areas where blood samples were collected for this study shows that both virus are widespread in the rural communities of Nigeria.
Human T-cell lymphotropic virus types I and II infections in mother-child paris in Nigeria
(Oxford University Press, 1999) Olaleye, D. O.; Omotade, O. O.; Sheng, Z.; Adeyemo, A. A.; Odaibo, G. N.
"A community-based survey to determine the prevalence of human T-cell Iymphotropic type I (HTLV-I) and type II (HTLV-II) virus infections in mothers and children in south-western Nigeria was carried out using blood samples collected in 1993. A multistage cluster, random sampling procedure was used to select 460 mother-child pairs (476 children because there were 16 sets of twills) from 14 enumeration areas. A commercially available, whole HTLV-I lysate antigen-based ELISA method was used to screen for HTLV-I and HTLV-II antibodies in the samples. A synthetic peptide antigen-based ELISA was then used to differentiate between antibody reactivity to either HTLV-I or HTL V-ll. Reactivity to HTLV-I or HTLV -II antibodies was found in 43 per cent (20/460) of mothers and in 1.1 per cent (5/476) of children in both rural and urban communities and all the positive children were males. None of the 16 sets of twins in this study was positive for either HTLV-I or HTLV-ll. Also none of the mother-child paired sera tested showed concordance for either HTLV-I or HTLV-II antibody positivity. The lack of concordance between mother and child sera suggests that vertical transmission may not be the major route of transmission of HTLV infection to children in south-western Nigeria. Other modes of transmission, such as the re-use of unsterilized needles for injections and surgical knives in local scarification, which are common practices in the region, need to be investigated as they may prove to be more important than vertical transmission. These findings have important implications for any control programme for diseases that can be spread by the same routes as HTL V infection (the human immunodeficiency viruses, hepatitis B, and hepatitis C infections)."
Human immunodeficiency seropositivity among mother-child pairs in South west Nigeria: a community-based survey.
(2001) Omotunde, O. O.; Olaleye, D. O.; Saliu, I.; Odaibo, N. G.; Adeyemo, A. A.
A community based survey to determine the prevelence of human immunodeficiency infection in Nigeira women and children in south western Nigeria is reported. A multi-stage cluster random sampling procedure was used to select mother-child pairs from 35 enumeration areas in south western Nigeria. The final study sample consisted of 460 mothers and 476 children (including 16 sets of twins). A commercially available recombinant antigen-based ELISA method was used to test for HIV-I and HIV-2 anti-body in sera and western blotting was used as a confirmatory test for initially reactive samples. Only one mother-child pair (out of 460 mother-child pairs) was found to the positive for HIV antibody giving a mother-child concordance for HIV infection of 0.22%. Antibody to either HIV-1 of HIV-2 was detected in 3.8% (18/476) of the children's sera and in 4.3% (20/460) of mothers sera. HIV-1 reactivity was commoner than HIV-2 reactivity (2.9% versus 0.8% among children and 2.8% versus 1.5% among mothers). There were many more positive samples in the rural than in urban areas among children (7.1% versus 1.1%) and also among mothers (6.8% versus 2.4%),(p<0.001). Ths, HIV infection appears to be a real problem in south western Nigeria. The lack of concordance between mother-child sera suggests that vertical transmission may not be a major route of tansmission of HIV infection in children in South western Nigeria. It suggested that certain high risk practices(such as the re-use of unsterillised hypodermic needles for injections and surgical knives in local scarfication) which are common practices, especially in rural areas, need to be investigated as potential major modes of transmission of the infection. Control programmes need to take note of these finidngs in order to adequatly paln comprhensive health education which will cover the whole population, invluding children.
Multiple presence and heterogeneous distribution of HIV-I subtypes in Nigeria
(Klober Academic Publishers, 2001) Odaibo, G. N.; Olaleye, O. D.; Ruppach, H.; Okafor, G. O.; Dietrich, U.
Human immunodefiency virus types I(HIV) subtypes circulating in Nigeria was determined by using the Peptide based Enzymes Immuno-Assay (PELISA) to anlayze sera or plasma samples collected from 925 individuals in southeastern and nothern) of Nigeria. The synthetic peptides used as the capture antigens in the PELISA were design from the consensus sequence of the thrid hypervariable region. (V3 loop) of HIV-I subtypes A, B, C, D, E and O of HIV-I. The assay was initially validated using plasma samples from individuals infected with various genetically identified HIV-I subtypes in Europe and AFrica. Any serum or plasma samples that reacted with more than one peptide was re-tested using the same antigen panel in a limiting ELISA technique. The result co- circulation of multiple HIV-I subtypes including A, B, C, D, E and O in Nigeria. Varying prevalence of specific antibodies to the six HIV-I subtypes included in the PELISA panel were detected among infected individuals (74), B=2.5%(23) and group O, 2.4%(20). Thirty-six (3.9%) of the samples from the northen and southeastern regions reacted with HIV-I subtype O and B peptides respectively. As far as it can be ascertained, this is the first report of dtection of HIV-I subtypes B, D, and E in Nigeria. Furthermore, the result of this work indicated widespread circulation of multiple HIV-I subtypes in Nigeria. Therefore a polyvalent vaccine will be the best option for effective prophylactic immunization against HIV-I infection in Nigeria.
Phylogenetic analysis of new hepatitis B virs isolates from Nigeria supports endemicity of genotype E in west Africa.
(Wiley-Liss, Inc, 2001) Odemuyiwa, S. O.; Mulders, M. N.; Oyedele, O. I.; Ola, S. O.; Odaibo, G. N.; Olaleye, D. O.; Muller, C. P.
"Isolates of hepatitis B viruses were collected from 20 acute and chronic hepatitis patients in a highly endemic region of Nigeria. Sequencing classified the isolates to the ayw4, as they all contained the amino acid variations characteristic for that serotype. In the pre-S2 region of five isolates, three to seven amino acids were deleted, suggesting that immune escape mutations previously associated only with chronic HBV infection may be observed also in acute disease. Phylogenetic analysis of the complete pre-S2/S (large S) genes (831 nt) demonstrated that all the viruses belonged to the same genotype E. So far, no isolates of genotvpe E have been found in any other region of the world, including the Americas. This may suggest a relatively recent introduction of this genotype into humans and would explain the relatively low genetic diversity of viruses belonging to this genotype. One genotype E virus had been found previously in a chimpanzee, and viruses betonging to the CHIMP genotype are related to other genotype E viruses. These findings are compatible with a transmission of genotype E viruses from chimpanzees to humans. "
Reproductive hormones in infertility and infection in sub-saharan African males
(2001) Charles-Davies, M. A.; Osotimehin, B. O.
The male factor is now recognised as a major contributor to a couples’ infertility. The role of reproductive hormones in male infertility is however controversial. This study therefore, was designed to investigate the role of reproductive hormones in male infertility in sub-Saharan Africa. 3 groups of subjects between 18-56 years were investigated. 25, 42 and 45 were recruited in fertile, infertile and sexually transmitted diseases (STDS). Follicle stimulating hormone (FSH), luteinising hormone(LH) and prolactin were estimated using the immunoradiometric assay technique while testosterone was estimated using radioimmunoassay technique utilizing commercially available kits (ICN Biomedical Inc.).Statistical analysis was done using students t-test and anova (one way) for comparison of means. FSH, LH, prolactin and testosterone were similar between fertile and infertile groups and between normospermic and dyspennic infertile groups. However, all except, prolactin were similar in STDs and fertile groups. Hormonal abnormalities may not be a major contributor to male infertility. However, role of prolactin in infertility and infection requires further studies.
Spermatozoal, seminal plasma and blood sperm antibodies in Nigerian males
(2001) Charles-Davies, M. A.; Osotimehin, B. O.
Infertility is common in Nigeria and the male role is now well recognized. Sperm antibodies (SA) have been observed as a cause of infertility and their production have in some circumstances been attributed to chronic infection of the genital tract. Sexually transmitted diseases (STDs) and infection-related infertility are reportedly highly prevalent in Nigeria. This study was therefore designed to evaluate the role of sperm antibodies and determine the involvement of STDs in the production of such SA among Nigerians. 122 adult males aged 18-56 years were investigated. 25 were normospermic, fertile males with no evidence of STDs and served as controls. 50 were infertile without STDs while 47 had proven STDs Immunobead binding technique was used for the detection of SA directly on the sperm cell, in seminal and blood plasma. Student’s t-test and anova (one-way) were used for statistical analysis of data obtained. Results showed that SA- IgG, IgA and IgM were present in blood and semen. However, mean percentage binding of these SA on motile sperm was low (<4%). Comparisons of SA in blood and semen between infertile/STDs groups and. fertile controls were not significantly different (p>0.05) The findings suggest that sperm antibodies are present but may not be associated with STDs or infertility in Nigeria males.
Antibodies to lassa virus Z protein and nucleoprtein co-occur in human sera from lassa fever endemic regions
(Medical Microbiology and Immunology, 2001) Gunther, S.; Kuhle, O.; Rehder, D.; Odaibo, G. N.; Olaleye, D. O.; Emmerich, P.; Meulen, J.; Schmitz, H.
It is not known whether the small 11-kDa Z protein of lassa virus is immunogenic during human lassa virus infection. To obtain evidence for the existence of an antibody response and to test the suitability of these antibodies for serosurveys, sera from lassa fever endemic regions(Guinea and Nigeria, n=75) were tested for co-reactivity to Z protein and nuclcoprotein (NP). Sera from a non-epidemic region (Uganda, n=50) served as a specificty control. Z protien and NP were expressed in Escherichia coli, affinity-purified, and used as antigen in western blot. Indiredt immunofluorescence (IIF) with lassa virus-infested cells was performed for comparison. Due to high unspecific reactivity of the African sera, western blot testing was performed with a 1:1,000 serum dilution. Under these conditions, none of the control sera but 12% of the sera from endemic regions co-reacted with both Z protein and NP. REactivity to Z protien was significantly associated with NP reactivity (p<10-6). Np and Z protein- specific antibodies were co-detected in 33% of the IIF-positive sera and in 5% of the IIF-negative sera (P=0.001). These data provides evidence for apperance of antibodies to Z protien and NP following Lassa virus infection. A recombination blot for detection of both antibody specificities seems to be specific but less sensitive than IIF.