FACULTY OF BASIC MEDICAL SCIENCES
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Item 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.Item 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.Item 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.Item 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).Item 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.Item 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.