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Biomedical subjects

J L Smart

Publications and source records attributed to J L Smart.

At least 37 records · Page 2Linked to original sources

Neuronal and synaptic measurements in the visual cortex of adult rats after undernutrition during normal or artificial rearing.

It is possible that the reported effects of early life undernutrition on brain morphology may be due to alterations in mother-infant interactions and not directly to undernutrition. We have investigated this possibility by comparing artificially reared with mother-reared rats. Four groups of black-and-white hooded male rats were reared. These consisted of mother reared control (MRC), mother reared undernourished (MRU), artificially reared control (ARC) and artificially reared undernourished (ARU). Artificially reared rats were raised in isolation away from their mothers from 5 to 21 days of postnatal age. They were fitted with a gastric cannula through which 'milk' was infused automatically. The period of undernutrition lasted from 5 to 25 postnatal days, following which the animals were fed ad libitum until 312 days of age. Rats from each group were then killed by perfusion with buffered 2.5% glutaraldehyde. Pieces of visual cortex from each rat were postfixed in osmium tetroxide and embedded in resin. Stereological procedures at the light and electron microscopical levels were used to estimate the synapse-to-neuron ratios in cortical layers II to IV. Both MRC and ARC rats had about 7000 synapses per neuron. However, this ratio was about 8300 in MRU rats whilst it was only about 5000 in ARU animals. The rearing x nutrition interaction was statistically significant at the 0.1% level. These changes in the synapse-to-neuron ratio were mainly due to alterations in the numerical densities of the synapses rather than that of neurons. These results demonstrate that environmental isolation, as a result of artificial rearing procedures, and concurrent undernutrition during the first three weeks of postnatal life, interact with one another to produce marked morphological changes in the adult rat brain. However, environmental isolation was not, by itself, sufficient to cause permanent changes in interneuronal connectivity.

Animals↗

Effects of early life undernutrition in artificially-reared rats: 3. Further studies of growth and behaviour.

Four groups of rat pups were reared: mother-reared control (well-fed) and undernourished (MRC, MRU) and artificially-reared control and undernourished (ARC, ARU). AR rats were fed expressed rats' milk (days 5-7), mixtures of rats milk and milk substitute (days 8-16), and milk substitute only (days 17-20) by intermittent infusion via a gastric cannula. Undernutrition, imposed from 5-25 days, was effected initially by underfeeding the mother (MRU) or by infusing restricted quantities of milk (ARU). Weaning was at 21 days and undernutrition from 21-25 days was by restricting the supply of solid food. All rats were fed ad lib from 25 days. From 18 weeks, male rats were subjected to 3 tests of behaviour: spontaneous alternation, conditioned food preference, and visual discrimination (Lashley stand). There were negative effects of both undernutrition and artificial rearing on body growth in weight and length. For two aspects of behaviour, preference for carbohydrate relative to protein (greater in U rats) and latency to jump (longer in U rats) the effects of early undernutrition were the same in both MR and AR animals. Hence, these effects cannot have been mediated through alterations in maternal care.

Animals↗

Epidermal growth factor advances some aspects of development but retards others in both rats and hamsters.

The present experiments were undertaken to confirm the recent suggestion that epidermal growth factor (EGF) can have both retarding and accelerating effects on development, using a greater number of developmental indices than hitherto; to extend such studies to another species, the golden hamster, and to compare the responses of males and females. On each of days 0-3, one male and one female rat pup from each of 16 litters of 6 pups were injected subcutaneously with human EGF (0.5 micrograms/g body weight), one male and one female with vehicle, and the remaining two pups were not injected. As expected, EGF accelerated incisor eruption and eye-opening. However, EGF retarded the detachment of the pinna and the appearance of the auditory startle response. Free-fall righting was little affected. Hamster litters were left undisturbed till day 7 to minimise infanticide. Thereafter, experimental design was as far as possible the same as for the rats. Pups from 18 litters were injected on days 7-10. EGF advanced eye-opening, but retarded auditory startling, vaginal opening and the weaning growth spurt. Free-fall righting was unaffected. Hence, EGF had similar accelerating and retarding effects on development in both rats and hamsters. Also, these effects were the same in males and females for most indices.

Analysis of Variance↗

Effects of early under-nutrition on dietary self-selection and relative carbohydrate- and protein-conditioned preferences.

Rats were either under-nourished from birth to 45 days and thereafter well fed, or were well-nourished throughout. Such previously under-nourished rats (PU) had a body weight deficit in adulthood of about 15% when compared with the well-fed group (C). On four training days, rats were presented with a distinctively odourized solution of carbohydrate or protein, following a 5-h period of food deprivation. On the test day, under the same food deprivation conditions as occurred during training, identical solutions distinguished only by their odour were presented simultaneously to the rats for a period of 20 min. PU rats showed a conditioned preference for the carbohydrate-paired odour. Control animals showed a small preference for the protein-paired odour. The same rats were later allowed to self-select from three macronutrients for a period of 8 days. No differences in dietary self-selection patterns were found between PU and C rats.

Animals↗

Influence of alpha 1-adrenergic receptor stimulation and phorbol esters on hepatic Na+/K+-ATPase activity.

The effects of the alpha 1-adrenergic agonist phenylephrine (PE) and the phorbol ester 4 beta-phorbolmyristate-acetate (PMA) on sodium pump function were studied in the rat liver. In order to distinguish between direct and indirect influences, ouabain-sensitive 86Rb uptake by intact liver slices was compared with ouabain-sensitive Na+/K+-ATPase activity in plasma membranes isolated from PE and PMA-perfused livers. At a buffer Ca2+ level of 2.5 mmol/l, PE (10 mumol/l) caused an initial stimulation of both 86Rb uptake and Na+/K+-ATPase activity followed at 5 min by a decrease in both activities. Both actions were blocked by the alpha 1-antagonist prazosin. The decrease in ouabain-sensitive Na+/K+-ATPase was paralleled by an increase in Mg2+ ATPase activity. At a Ca2+ level of 1.5 mmol/l, PE stimulation of 86Rb uptake and Na+/K+-ATPase was sustained, and the inhibitory component was not expressed. PMA (4 mumol/l) reduced 86Rb uptake and Na+/K+-ATPase and similar to PE, this inhibition was paralleled by an increase of Mg2+-ATPase activity. 4 alpha-PMA, which does not activate protein kinase C, failed to influence 86Rb uptake or Na+/K+-ATPase. These results demonstrate that PE and PMA effects on ouabain-sensitive 86Rb uptake are preserved in isolated membranes, indicating a direct influence on the Na+/K+-ATPase. A role for protein kinase C in modulating sodium pump activity is suggested.

Adrenergic alpha-Agonists↗

Effects of early life undernutrition in artificially-reared rats. 2. Subsequent behaviour.

Four groups of rat pups were reared: mother-reared control (well-fed) and undernourished (MRC, MRU) and artificially-reared control and undernourished (ARC, ARU). AR rats were fed expressed rats' milk (days 5-7), mixtures of rats' milk and milk substitute (days 8-16), and milk substitute only (days 17-20) by intermittent infusion via a gastric cannula. Undernutrition, imposed from 5-25 days, was effected initially by underfeeding the mother (MRU) or by infusing restricted quantities of milk (ARU). Weaning was at 21 days and undernutrition from 21-25 days was by restricting the supply of solid food. All rats were fed ad lib from 25 days. From 18 weeks, male rats were subjected to 3 behavioural tests: open field, social behaviour (encounters between rats of like treatment group) and bar-pressing for food (CRF, FR5, VI 1', VI 2' and Extinction). Previously undernourished rats responded at higher rates on FR5, received fewer rewards on VI 2' and displayed more aggression during social interaction. These findings may reflect direct effects of nutrition on brain growth. In the open field and social situations ARU were generally less active than ARC animals, whereas MRU and MRC rats differed little. These results are discussed in terms of MRU pups being maternally "buffered" against the worst effects of undernutrition and ARC rats displaying characteristics of "early stimulated" animals.

Animals↗

Poultry waste associated type C botulism in cattle.

Botulism in UK cattle has been confirmed by demonstrating type C botulinum toxin in sera from affected animals. Evidence is presented indicating the source of intoxication to be poultry carcasses containing type C Clostridium botulinum and its toxin. The organism was also found in poultry litter and in alimentary tract samples from slaughtered animals. The implications of these findings are discussed.

Animal Feed↗

Growth and development of rats artificially reared on rats' milk or rats' milk/milk-substitute combinations.

Rat pups were artificially reared (AR) from post-natal day 5 by intermittent gastric infusion. Mother-reared (MR) siblings served as controls. Fourteen measures of body and organ growth were taken at the end of each experiment. In Expt 1, two batches of pups were given rats' milk only, obtained by manual expression from anaesthetized dams. The first batch, reared to 12 d, grew less well than the MR group, probably because they received too little milk. However, relative to body-weight, organ weights were as great or greater than those of MR pups, except for heart weight. The second batch, given more milk and reared to 20 d, showed no deficits in organ or body-weights, but excesses in kidney, gastrocnemius muscle, stomach and caecum weights. There were no losses from 'bloat', a condition of gastrointestinal distention often encountered in artificial rearing with milk substitutes. Obtaining rats' milk is extremely labour-intensive and in Expt 2, more economical regimens were devised in which pups were started off on expressed rats' milk and then changed to a milk substitute resembling rats' milk in composition, either abruptly at 12 d or gradually between 8 and 17 d. Both regimens were successful, in that there were no losses from bloat and most measures of growth were at least as great as in the MR group. Only heart weight was lower in both AR groups and adrenal weight in the abruptly changed AR group. The weights of the stomach and caecum and the length of the small intestine were all high in both AR groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

Effects of early-life undernutrition in artificially reared rats: subsequent body and organ growth.

1. Four groups of rat pups were reared: mother-reared (MR) control (well-fed) and undernourished (MRC and MRU respectively) and artificially reared (AR) control and undernourished (ARC and ARU respectively). Pups for artificial rearing were fitted with a gastric cannula on postnatal day 5 and were fed, by intermittent gastric infusion, expressed rats' milk (days 5-7), mixtures of rats' milk and milk-substitute (days 8-16), and milk-substitute only (days 17-20). Solid food was available to MR pups throughout and to AR pups from day 14. Undernutrition, imposed from postnatal days 5 to 25, was effected initially by underfeeding the mother (MRU) or by infusing restricted quantities of milk (ARU). Weaning was at 21 d and undernutrition from day 21 to day 25 was by restricting the supply of solid food. All rats were fed ad lib. from 25 d. 2. The developmental milestone, eye-opening, was delayed by undernutrition but unaffected by artificial rearing. 3. Growth curves in body-weight during the refeeding phase were influenced most by previous undernutrition and to a lesser extent (also negatively) by artificial rearing. 4. Fourteen measures of body and organ growth were taken at autopsy at 39 weeks. Twelve measures were affected by nutrition and only four by rearing (weight of whole body, epididymal fat pads, renal fat pads and adrenals). 5. AR rats had lighter epididymal and renal fat pads than MR rats perhaps due to the low fat content of the expressed milk they received early in artificial rearing.

Adipose Tissue↗

Incidental learning is impaired during early-life undernutrition.

Rats were either well-nourished (control) or undernourished (PU) during the suckling and early post-weaning periods (birth to 45 days), after which all animals were fed ad libitum. From 25 to 45 days half of the rats in each group were exposed continuously in their home cases to shape stimuli (triangles and circles). Half of each of these 4 groups were given "reminders" of the stimuli through exposure for 2 h every 10-12 days from 55 to 131 days. Beginning on day 132, ability to discriminate these same visual stimuli was tested using a nonappetitively motivated version of the Lashley jumping stand technique. Discrimination learning per se was unimpaired by previous undernutrition (control and PU rats not viewing the stimuli prior to training performed equally well). However, early-life exposure led to improved learning performance only in control rats; it had no effect on the performance of PU rats (significant exposure X nutrition interaction). These findings indicate that undernutrition interfered with early "incidental learning", that is, learning about features of the environment which are not, at the time, biologically relevant. Finally, retention of the discrimination was assessed 9 weeks after the rats had attained criterion performance. There were no effects of nutrition or prior exposure on long-term memory.

Animals↗

A phenomenon: left-biassed asymmetrical eye-opening in artificially reared rat pups.

From 4 or 5 postnatal days, rat pups were either reared by their mothers (MR) or artificially reared (AR) without their mothers by infusion of 'milk' through a gastric cannula. In AR, but not MR, pups the left eye was more likely to open first than the right eye (P less than 0.001). The left-biassed eye-opening of AR pups may be a manifestation of stress-induced lateralisation of their brains.

Animals↗

Differences in the role of Na+/K+-ATPase during alpha 1-adrenergic events in rat and rabbit aorta.

Transport activity of the Na+/K+-ATPase was studied in rat and rabbit aorta under basal and agonist-stimulated conditions. Basal ouabain-sensitive 86Rb+ uptake was 2.9-fold higher in rat tissues as compared to rabbit tissues. This higher uptake in the rat was associated with a greater sensitivity to the Na+/H+ exchange inhibitor amiloride. Stimulation of alpha 1-adrenergic receptors by norepinephrine (NE) or phenylephrine (PE) resulted in an increase in ouabain-sensitive 86Rb+ uptake, whose temporal pattern differed between arteries of the two species. In rat aorta the increase was maximal during the first 2 min of agonist exposure reaching approximately a 50% higher rate of uptake than controls while rabbit aorta exhibited a steady rise in 86Rb+ uptake. Removal of extracellular Ca2+ by EGTA (1 mM) for 10 min resulted in an activation of Na+/K+-ATPase-related 86Rb+ uptake after which PE was still capable of causing a further increase, suggesting that Ca2+ influx is not responsible for the receptor-induced stimulation. Removal of extracellular Na+ reduced the PE-induced stimulation, while amiloride did not block the agonist effect. To characterize the role of the Na+/K+-ATPase during contractile events, receptor-induced 45Ca2+ uptake, 45Ca2+ release and contraction were compared in rat and rabbit aorta following Na+/K+-ATPase inhibition. Rat responses to PE were readily inhibited by ouabain or K+-free conditions, while rabbit responses were relatively resistant. 45Ca2+ extrusion and relaxation following alpha 1-adrenergic receptor stimulation were both highly dependent on activity of the Na+/K+-ATPase in rat aorta. These species' differences in Na+/K+-ATPase transport activity and its role in the regulation of contractility illustrate an example of heterogeneity in the ionic control of arterial tone.

Animals↗

Type of milk substitute influences growth of the gastrointestinal tract in artificially reared rat pups.

Growth of the gastrointestinal (GI) tract was studied in rat pups that were reared normally (mother-reared, MR) or were artificially reared (AR) by intragastric infusion of milk substitutes from postnatal day 5. Two milk substitutes were used: one high in carbohydrate and low in protein compared with rat's milk (Messer) and the other close in composition to rat's milk (Auestad). Pups reared on these formulae are termed ARM and ARA, respectively. Pups were killed at 7, 12, and 20 days for the determination of the wet and dry weights of stomach and caecum and the lengths of the small and large intestines (SI and LI). At 7 days AR pups showed deficits in several GI measures compared with MR rats. However, by 20 days they showed enhanced growth of various parts of the GI tract. Stomach weight was greatest in ARA rats; caecum weight was greater in AR than in MR rats; SI was longer in AR than MR rats, with the effect more pronounced in ARM rats. These effects were already evident, or becoming so, by 12 days. In an additional experiment, rats were AR on rat's milk from 5 to 12 days. Their GI tracts did not differ from MR, suggesting that the AR procedure per se was not responsible for the above GI growth effects.

Animals↗

Lack of correlation between [3H]ouabain binding and Na-K ATPase inhibition in rat aorta.

The binding of [3H]ouabain to intact strips of rat aorta was compared with the ability of ouabain to inhibit the uptake of 86Rb by the same preparation. When a cold temperature wash was used to process tissues after binding of [3H]ouabain, a class of relatively high affinity binding sites was found (KD = 1.2 X 10(-7) M). Binding was saturable and sensitive to both ATP depletion and elevated potassium. Elevation of cytoplasmic Ca2+ levels by phenylephrine or c-AMP levels by theophylline and terbutaline had no influence on [3H]ouabain binding. Ouabain inhibition of 86Rb uptake progressed to 60% of the total 86Rb uptake at 2 X 10(-3) from a threshold of about 10(-5) M. Half-maximal inhibition by ouabain occurred at a concentration of 10(-4) M. The disparity between [3H]ouabain binding and inhibition of 86Rb uptake indicates that the high affinity binding site in the rat does not contribute to inhibition of Na-K ATPase function.

Animals↗

Mating behaviour of male rats following pre- and early postnatal undernutrition: a comparison of two outbred stocks.

Developing rats of two outbred stocks (Lister and Wistar) were either well-nourished or were undernourished by feeding their mothers a restricted quantity of food during pregnancy and lactation. All rats were fed ad lib from 25 days. Beginning at 14 months, the mating behaviour of males was investigated in five tests at weekly intervals using ovariectomised females brought into behavioural oestrus using injections of oestradiol and progesterone. Lister males were tested with Lister females, and Wistar males with Wistar females. Early life undernutrition reduced the numbers of non-penetrative mounts and shortened the latency to ejaculate in rats of the Lister but not the Wistar stock. Mount latency was reduced by early undernutrition in the Wistar stock, but was unaffected in the Lister stock. These results indicate that the effects of early life undernutrition on male mating behaviour differ in detail from one stock of rat to another. In general, however, the results suggest that infantile undernutrition facilitates, rather than impairs, the sexual behaviour of male rats in "middle-age."

Animals↗

Growth and development of rats artificially reared on different milk-substitutes.

Rat pups were artificially reared (AR) from postnatal day 4 or 5 till day 20 or 21, by fitting them with gastric cannulas through which milk-substitutes could be infused automatically. Three milk-substitutes were compared: milk M, the usual diet for AR studies, which was somewhat low in protein and very high in carbohydrate; milk A, which resembled rats' milk much more closely in composition; and milk isoM, which was based on the high-energy milk M but was made isoenergetic with milk A. Pups given these diets were termed ARM, ARA and ARisoM respectively. Siblings of the AR rats were left with their mothers to form a mother-reared (MR) control group. Rats were autopsied at 20 or 21 d. Growth in body-weight of all groups of AR pups lagged behind that of their MR siblings for about the first week of AR, but the ARM group showed complete catch-up and the ARA group partial catch-up in body-weight during the second week. ARisoM rats were growth-retarded throughout. Inspection of organ weights expressed relative to body-weight revealed disturbances of organ growth in all AR groups compared with MR animals. ARM rats showed excessive epididymal fat pad and liver weights, but deficits in gastrocnemius muscle, heart and adrenal weights. In contrast, ARA rats usually displayed increased spleen and stomach weights, but lower weight of interscapsular brown adipose tissue. ARisoM rats had high brain, liver and stomach weights and low muscle and spleen weights relative to body-weight. All AR groups had elongated small intestines. Hence the patterns of abnormal organ growth differed between groups. Those shown by the ARM and ARisoM groups seemed the more seriously abnormal. The diet approximating the composition of rats' milk (milk A) appears, as intended, to be an improved milk-substitute.

Animal Nutritional Physiological Phenomena↗

Predicting mothers' choice of infant feeding method.

There is relatively little published research concerning the relationship between mothers' attitudes towards methods of feeding infants and their choice of breast-feeding or bottle-feeding as methods of feeding their own babies. The present study used Fishbein & Ajzen's theory of reasoned action to analyse the impact of the attitudes, perceived norms and beliefs of 50 primiparous mothers on (i) their intentions to breast-feed or bottle-feed, assessed antenatally; and (ii) their self-reported use of breast-feeding and bottle-feeding during the first six weeks of the baby's life. The findings were generally consistent with the theory of reasoned action. Attitudes to the infant feeding methods accounted for a large and significant amount of variation in infant feeding behaviour. However, there were some aspects of the findings that were not entirely consistent with the theory. Attitudes to behaviour contributed significantly and independently to the prediction of behaviour, and beliefs about the consequences of behaviour explained a near-significant amount of variation in intentions, beyond that already accounted for by attitudes and normative beliefs. Theoretical and practical implications of these findings are discussed.

Adolescent↗