The effect of post-natal malnutrition on pepsinogen secretion receptors in weanling rats

Post-natal malnutrition was induced in rats using the expanded litter model. Pepsinogen secretion of isolated gastric glands in response to several secretagogues was measured. Malnourished 19-day-old pups showed no response to carbachol, CCK-8, gastrin, secretin and ionophore A23187 compared to well-nourished animals, but showed comparable secretion of pepsinogen after stimulation with dibutyryl cAMP (DiBcAMP). Hydrocortisone treatment for 48 h caused increased pepsinogen accumulation and elevated pepsinogen secretory responsiveness to carbachol and secretin of gastric glands isolated from post-natal malnourished pups. Our results indicate that isolated gastric glands obtained from well-nourished rat possess two functionally distinct receptors for gastrin and C-terminal fragment of CCK. Our study supports the concept that in malnourished rats there is a decreased number of binding sites or/and some post-receptor defects. Pepsinogen release mechanisms remain unaffected.     

Influence of perinatal malnutrition on adult physiological and behavioral reactivity in rats

A series of experiments examined the behavioral and pituitary-adrenal response to novelty of perinatally malnourished rats tested as adults after nutritional rehabilitation begun at weaning. Neither the behavioral measures of ambulation, rearing and defecation, nor the plasma corticosterone response to a brief exposure to an open field differentiated the previously malnourished subjects from controls. Similar to controls, previously malnourished subjects were also capable of displaying a graded corticoid elevation to environments increasingly different from the home cage. However, exploratory behavior, as measured by head-dip frequency and duration in the hole-board, was reduced in the previously malnourished rats. Although latency and amount of fluid consumed in a novel environment did not differ, previously malnourished rats were unable to use the cues associated with a consummatory behavior to modulate the pituitary-adrenal response to novelty. Thus, perinatal malnutrition does not influence either the behavioral or physiological activational response to novel stimulation but appears to alter the ability of the animal to use a consummatory behavior to modulate this response.     

Hyposensitivity to serotonergic stimulation in protein malnourished rats

Rats subjected to early protein malnutrition have higher levels of brain serotonin (5-HT) than well-nourished rats. In the present study we asked whether the elevated 5-HT levels of associated with any changes in sensitivity to serotonergic stimulation. In four different behavioral tets the effects of the 5-HT agonist N,N-dimethyltryptamine (DMT) were, with only a few exceptions, smaller in rats malnourished during both pre- and postweaning stages of development or during just one period or the other. In Experiment 1 the 5-HT syndrome induced by DMT was weaker in malnourished rats than in well-nourished ones. In Experiments 2 and 3, DMT was not a disruptive to malnourished rats in two motor tasks, rotating rod and treadmill, as it was to rats reared under high protein conditions. In Experiment 4 reductions in acoustic startle amplitudes induced by DMT were not as large in malnourished as in well-nourished rats. The hyposensitivity to DMt in protein malnourished rats may reflect a diminished sensitivity of 5-HT receptors resulting from the abnormally high levels of the neurotransmitter.     

The effect of triiodothyronine on evanescent delayed hypersensitivity to sheep red blood cells and on the primary antibody response to trinitrophenylated Brucella abortus in severely undernourished weanling mice

Two experiments were conducted using weanling male CBA/J mice. Animals were fed for 14 days a nutritionally complete diet, either ad libitum, or in restricted amounts such that they lost about 30% of their weaning weight during the feeding period. Half the animals from each food intake group received 0.2 mg triiodothyronine (T3)/kg diet. Evanescent delayed hypersensitivity to sheep red blood cells (SRBC) was depressed by malnutrition but not influenced by T3 supplementation. T3 increased nucleated spleen cell number in mice immunized with trinitrophenylated Brucella abortus (TNP-BA). The number of splenic anti-TNP direct plaque-forming cells (PFCs) was decreased by malnutrition when expressed on a per spleen basis. T3 supplements increased splenic PFC number of malnourished mice when results were expressed either per spleen or per 10(6) cells, and increased PFCs per spleen in well-nourished mice. Serum anti-TNP agglutinin titres were unaffected by malnutrition and by T3. The results extend our previous observations as to the improvement by T3 of the primary anti-SRBC antibody response of malnourished weanling mice, and suggest that therapeutic hormonal treatment could be used to improve antibody responses of malnourished individuals. The mechanism of the effect of T3 is unknown, but the lack of effect on delayed hypersensitivity to SRBC implies that T3 (when administered at the dosage of the present protocol) acts on only some immune cells and does not exert a generalized adjuvant effect.     

Malnutrition and experimental lung allergy

Background Although it is commonly accepted that the immune response is affected by malnutrition there are very few data about its effect in allergie diseases. Objective The aim of the present study was to investigate the effect of malnutrition in allergic lung inflammation. Methods An anaphylactic reaction was induced in rat lungs and the increased vascular permeability was measured in the trachea, internal and external bronchi and parenchyma by the Evans blue extravasation method. These studies were conducted in two dietary groups: one fed a normoproteic diet (18%) and the other a hypoproteie diet (4.5%). When the animals were 60 days old the group fed the hypoproteie diet presented a reduction of 77.86% in bodyweight, 63.3% in food intake and 36% in plasma protein concentration characterizing a severe protein-calorie malnutrition. Results The anaphylactic reaction in the lungs induced a significant increase in vascular permeability in the trachea and bronchi of both dietary groups. However, the intensity of this effect was significantly lower in the malnourished group. Analysis of immunoglobulin isotypes in the serum by ELISA showed that whereas IgG1 and IgG2a levels were similar in both groups, the levels of IgE were significantly lower in the malnourished animals. Moreover, the levels of antigen-specific IgG1, IgG2a and IgE were all significantly inhibited by the protein-calorie malnutrition. When antibodies were passively transfered to the malnourished rats, they developed a reaction as intense as the normoproteic group. Conclusions These results suggest that the capacity to release infiammatory mediators and the vascular response to these mediators is not affected by this type of malnutrition and, therefore, the diminished response of the airways reported here is probably due to the lower levels of anaphylactie antibodies produeed by the malnourished rats.     

The dorsolateral thalamus as a relay in the retino-wulst pathway in pigeon (Columba livia)

Summary In 4 dorsolateral thalamic nuclei (LA, DLAmc, DLLd and DLLv) short latency evoked responses were recorded after electrical or photic stimulation of the contralateral eye. Electrical stimulation of these 4 nuclei led to bilaterally evoked responses in the wulst, where previous experiments had demonstrated an oligosynaptic projection from the retina.Cooling in DLL, while stimulating the contralateral optic nerve, leads to a severe decrement of both wulst responses suggesting that the thalamus functions as a relay within the retino-thalamo-hyperstriatal pathway. When the optic nerve ipsilateral to the cooled thalamus is stimulated the ipsilateral wulst response is unchanged while the contralateral wulst response is enhanced, suggesting a disinhibition. Similarly an inhibitory effect of the thalamus on one side upon the contralateral wulst response was found after concomitant stimulation of one optic nerve and a delayed stimulation of the ipsilateral thalamus.The dorsolateral thalamic group is the origin of bilateral wulst projections, the pathway to the contralateral telencephalon was demonstrated to pass via the supraoptic decussation DSO. Cooling DSO diminished the inhibitory thalamic effect upon the contralateral wulst. DSO was corroborated as part of the ipsilateral retino-wulst system.Abbreviations DLAmc Nucleus dorsolateralis anterior, thalami, pars magnocellularis - DLL Nucleus dorsolateralis anterior thalami, pars lateralis - DLLd DLL, pars dorsalis - DLLv DLL, pars ventralis - DSO Decussatio supraoptica - E Ectostriatum - GLv Nucleus geniculatus lateralis, pars ventralis - LA Nucleus lateralis anterior thalami - N Neostriatum - ON Optic nerve - Rt Nucleus rotundus - TeO Tectum opticum - W Wulst Supported by Grants Nos. 3.329.70 and 3.823.72 of the Swiss National Foundation for Scientific Research and by the Dr. Eric Slack-Gyr Foundation.A preliminary report was given at the Union Schweizerischer Gesellschaften für Experimentelle Biologie, May 6, 1972 in Geneva (Meier et al., 1972b).     

Prenatal malnutrition and sleep states in adult rats: effects of restraint stress

Independently, prenatal malnutrition and psychological/physical stress have been shown to affect sleep architecture in adult rats. As malnutrition and stress commonly co-exist in malnourished human populations, the objective of the present study was to ascertain the combined effects of these two insults by examining sleep-wake parameters following a brief restraint stress in prenatally protein malnourished rats. The male offspring of rats provided with a protein deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy were implanted with recording electrodes beginning at postnatal day 90. Polygraph recordings were obtained to quantify sleep states during the first 4 h of the dark phase of the cycle on 2 consecutive days. The first followed a 24-h habituation session to the recording chamber (baseline). The second occurred at the same time of day but followed 20 min of restraint stress in a Plexiglas tube. During baseline, prenatally malnourished rats spent more time in rapid eye movement sleep (REMS) in the first 2 h after "lights off" (block 1), and greater amounts of wakefulness (W) with a corresponding reduction in slow wave sleep (SWS) in the second two hours (block 2), as compared with controls. Following stress, the sleep architecture of both groups of rats remained unaltered in block 1 relative to their baseline day. In block 2, both groups exhibited significant reductions in SWS and REMS with significantly greater reductions being expressed in the prenatally malnourished group (most dramatically, REMS was completely eliminated). These findings suggest that sleep disturbances may be more severe in those malnourished human populations subjected to acutely stressful experiences.     

Prenatal protein malnutrition alters response to reward in adult rats

Developing rats were either malnourished or adequately nourished during the prenatal period by feeding their dams diets of 6% (low) or 25% (adequate) casein content 5 weeks prior to mating and throughout pregnancy. All pups received adequate nutrition from the day of birth onwards. In Experiment 1, male offspring aged 125 days were tested in a food-rewarded variable interval 2-min (VI 2') operant paradigm under three levels of body weight reduction (90%, 85% and 80% of their ad lib feeding weight). Previously malnourished rats showed significantly higher response rates than well-nourished controls at the 90% and 85% levels but not at the 80% level. In Experiment 2, behaviorally native male littermates aged 225 days were tested in a saccharin-solution-rewarded VI 2' operant task. The rate of receipt of reward within each daily session was found to differ in the two nutritional groups. Previously malnourished rats maintained a stable rate of reward throughout the session while the controls showed a rapid decline over the first 15-20 min. The higher rate of reward late in the session in Experiment 2 and the elevated response rate in the first two phases of Experiment 1 suggests that prenatal protein malnutrition increases subsequent responsiveness to reward.     

Effects of early malnutrition on tail pinch-induced behavior of the rat

To determine if rats malnourished early in life are hyperresponsive to aversive stimulation their responses to tail pinch were measured in three experiments. Early malnutrition was induced by feeding the mothers an 8% casein diet from 5 weeks before mating until the pups were weaned at 21 days of age. Well-nourished offspring were born to mothers fed a 25% casein diet. At weaning half of the pups in each group were switched to the other diet. They were 60–100 days old when tested. Neither the latency to the first response elicited by tail pinch nor the total duration of stimulus-bound behavior indicated that the rats malnourished as preweanlings were hyperresponsive. In all three experiments, however, rats subjected to early malnutrition responded differently than well-nourished animals, irrespective of the dietary treatment at the time of testing. Malnourished rats gnawed more than they licked food and other objects; well-nourished rats did the opposite. Measurements of food weights confirmed the observation that eating was an infrequent rather than a predominant behavior.     

Effects of moderate and severe malnutrition in rats on splenic T lymphocyte subsets and activation assessed by flow cytometry

Malnutrition is distributed widely throughout the world and is a particular problem in developing countries. Laboratory animals have been very useful in studying the effects of varying levels of malnutrition because non-nutritional factors that affect humans may be controlled. The objective of the present study was to determine the effects of moderate and severe malnutrition on lymphocyte proportions and activation markers of T cells in experimentally malnourished rats during lactation by flow cytometry. Lower absolute (total) and relative (%) numbers of CD3+ and CD4+ lymphocyte subpopulations were observed in moderately (second degree) and severely (third degree) malnourished rats compared with well-nourished rats (P < 0.05). Both groups of malnourished rats showed a significant decrease in the percentage of CD71+ cells at 24 h post-activation with phytohaemagglutinin (PHA). After 24 h activation of spleen cells with PHA, a lower percentage of CD25+ cells was observed in malnourished than well-nourished rats (P < 0.05). In conclusion, the results of this study indicated an altered expression of CD71 and CD25 during activation of T lymphocytes in malnourished rats and may partially explain increased susceptibility to infection associated with malnutrition. Moreover, these results demonstrated that moderate malnutrition affects the response of T lymphocytes as much as severe malnutrition.     

Early postnatal protein malnutrition changes the development of social play in rats

Early protein malnutrition produces structural and functional alterations in the brain and changes the organism-environment interactions. Rats from 26 to 76 days of age were used to study the effects of early postnatal protein malnutrition on the development of social play. During lactation phase the litters were fed diet containing 16% protein (well-nourished) or 6% protein (malnourished). From weaning to the end of behavioral tests well-nourished animals were fed a commercial lab chow diet (well-nourished--W) and the malnourished rats were divided into 2 groups: one was maintained on 6% protein diet (malnourished--M) and the other was fed a commercial lab chow diet (previously malnourished--PM). Pairs of male rats of same diet conditions were tested, at different ages, for three consecutive days. During sessions the following behaviors were recorded: pinning, wrestling, walk-over and rear. The frequency of wrestling and walk-over was significantly higher in malnourished as compared to well-nourished animals (p<0.05). Early protein malnutrition also changed the ontogeny of play behaviors (pinning and wrestling) with developmental retards in M and PM as compared with W animals, especially at 46 and 56 days of age. These results suggest that early protein malnutrition can affect the development of neural mechanisms underlying social play in rats.     

Electrophysiological evidence for axonal sprouting of cerebellothalamic neurons in kittens after neonatal hemicerebellectomy

Summary Changes in cerebello-cerebral responses after hemicerebellectomy were investigated in 19 kittens by laminar field potential analysis in the cerebral cortex. In all of 11 kittens operated on before 11 days of age and kept for more than 16 days after surgery, marked cerebello-cerebral responses were evoked not only contralaterally as in intact animals but also ipsilaterally. In none of 16 intact kittens ranging in age from 2 to 14 days was there a detectable response in the cerebral cortex to stimulation of the ipsilateral cerebellar nucleus.Pathways responsible for the ipsilateral cerebello-cerebral responses were investigated by destruction of the thalamic VL nucleus and by unitary recordings from cerebellar nuclear neurons with antidromic activation on stimulation of the thalamus. From the latter investigation, a remarkable increase in the number of neurons with bilateral projections upon the thalamus was seen in the surgically treated kittens. Stimulation of the VL thalamic nucleus contralateral to the remaining hemicerebellum induced a marked response in the frontal cortex not only ipsilaterally as in intact animals but also contralaterally. The latter response was considered to be mediated by an axon reflex of the bilateral projection neurons. Destruction of that VL nucleus abolished the contralateral cerebello-cerebral response whereas the ipsilateral cerebello-cerebral response remained unchanged.It is concluded, that in kittens, hemicerebellectomized in the early postnatal period, nuclear neurons in the remaining cerebellum sprout axon collaterals growing into the thalamus ipsilateral to the spared hemicerebellum and that these sprouting axon collaterals make synapses on the thalamic neurons projecting upon the cerebral cortex.     

The use of habituation in the study of the effects of infantile malnutrition.

Habituation of the orienting response (OR) was used to assess possible attentional deficits associated with infantile malnutrition. The procedure involved the presentation of 40 trials of a pure tone stimulus to 8 marginally nourished and 8 malnourished 13 1/2-month-old male infants. The results showed that the initial OR to stimulus onset, as measured by the magnitude of cardiac deceleration, was significantly larger in marginally nourished than in malnourished infants. Within-group comparisons revealed that marginally nourished infants showed significant increases in OR magnitude to changes in tonal frequency whereas the malnourished infants did not. The results were taken as evidence of an attentional deficit associated with infantile malnutrition that is likely to interfere with subsequent learning.     

Effect of electrical stimulation of the reticular nucleus of the rat thalamus upon c-fos immunoreactivity in the retrosplenial cortex.

Electrical stimulation of the reticular nucleus of the rat thalamus results in activation of c-fos immunoreactivity in nerve cells of the ipsilateral retrosplenial cortex. The c-fos immunoreactive neurons are mainly concentrated in lamina IV of the retrosplenial cortex. Conversely, electrical stimulation of the retrosplenial cortex induced c-fos immunoreactivity in the ipsilateral reticular nucleus of the thalamus. The results of the electrical stimulation suggest a direct synaptic connection between the cerebral cortex and the ipsilateral reticular thalamic nucleus. Simultaneous immunohistochemical staining proves that the majority of nerve cells and dendro-dendritic terminals in the reticular thalamic nucleus contain parvalbumine and, at the same time, also GABA. The role of GABA-ergic parvalbumine immunoreactive terminals in the reticular thalamic nucleus seems to be related to integration and processing of impulses and attentional gating, distinguishing between noxious and innocuous inputs.     

Induction of high frequency activity in the somatosensory thalamus of rats in vivo results in long-term potentiation of responses in SI cortex

Summary Extracellular single-unit techniques were employed to record unitary activity simultaneously from the thalamic ventral posterior medial (VPM) nucleus and the ipsilateral primary somatosensory cortex of adult rats. Cross-correlation analysis triggered by the spontaneous firing of thalamocortical relay neurons in VPM and the discharge of layer IV neurons in the corresponding ipsilateral cortical barrel indicated that the paired-units included in this study were strongly correlated in their activity. The baseline responses of highly correlated cortical/thalamic pairs to a 10 ms deflection of a vibrissa on the contralateral side were measured using poststimulus time histograms. After establishing the baseline response, high frequency activity in VPM was induced in one of two ways: i) direct electrical stimulation of thalamic neurons or ii) whisker stimulation in the presence of bicuculline methiodide (BIC) released near the thalamic neurons. Both methods resulted in a conditioning stimulus (CS) paradigm consisting of bursts of high-frequency activity (50–100 Hz) with an inter-burst interval of 150 ms (7 Hz). Almost immediately following the presentation of the CS, the response of layer IV cortical neurons to vibrissa stimulation increased by 37–62% over baseline values, which was maintained after the effects of BIC had worn off in VPM. This enhancement in the response of the cortical neurons was not accompanied by a concomitant increase in the thalamic responses. Thus, these results strongly suggest that the potentiation first occurred at the thalamocortical synapse.     

Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli.

Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation.     

Hospital malnutrition and inflammatory response in critically ill children and adolescents admitted to a tertiary intensive care unit

Critical illness has a major impact on the nutritional status of both children and adults. A retrospective study was conducted to evaluate the incidence of hospital malnutrition at a pediatric tertiary intensive care unit (PICU). Serum concentrations of IL-6 in subgroups of well-nourished and malnourished patients were also evaluated in an attempt to identify those with a potential nutritional risk. METHODS: A total of 1077 patients were enrolled. Nutritional status was evaluated by Z-score (weight for age). We compared mortality, sepsis incidence, and length of hospital stay for nourished and malnourished patients. We had a subgroup of 15 patients with severe malnutrition (MN) and another with 14 well-nourished patients (WN). Cytokine IL-6 determinations were performed by enzyme-linked immunosorbent assay. RESULTS: 53% of patients were classified with moderate or severe malnutrition. Similar amounts of C- reactive protein (CRP) were observed in WN and MN patients. Both groups were able to increase IL-6 concentrations in response to inflammatory systemic response and the levels followed a similar evolution during the study. However, the mean values of serum IL-6 were significantly different between WN and MN patients across time, throughout the study (p = 0.043). DISCUSSION: a considerable proportion of malnourished patients need specialized nutritional therapy during an intensive care unit (ICU) stay. Malnutrition in children remains largely unrecognized by healthcare workers on admission. CONCLUSIONS: The incidence of malnutrition was very high. Malnourished patients maintain the capacity to release inflammatory markers such as CRP and IL-6, which can be considered favorable for combating infections On the other hand, this capacity might also have a significant impact on nutritional status during hospitalization.     

The response of malnourished babies to cold

1. Twelve malnourished Jamaican children, aged 4-16 months, were studied before and after treatment, to see whether malnutrition impaired their response to cold.2. When they were studied in the post-absorptive state and in a neutral thermal environment, they had a lower rate of oxygen consumption per kg body weight, a slower pulse rate, lower body temperatures, lower R.Q., and evidence of a smaller peripheral blood flow on admission to hospital than they did after recovery.3. The malnourished children failed to increase their heat production above resting levels at 25 degrees C, and their rectal temperature fell at a rate of 1 degrees C/hr in spite of a further decrease in peripheral circulation.4. When they had recovered they maintained their body temperature within the normal range on exposure to this temperature, while increasing their heat production by 20%. The thermogenesis was apparently of the non-shivering type.5. There was evidence of increased metabolic activity in the interscapular brown fat pad at 25 degrees C both on admission and before discharge. In the malnourished children this activity was not sufficient to produce a measurable increase in total oxygen consumption.6. Interscapular brown fat was examined at autopsy in thirteen malnourished and fifteen well nourished children aged 1-24 months. Lipid depletion was found in this tissue in the former but not in the latter. This may explain the impaired response of the malnourished child to cold.     

Assessment of DNA damage in spleen, bone marrow, and peripheral blood from malnourished rats by single cell gel electrophoresis assay

Severe malnutrition is widely distributed throughout the world and exhibits a high prevalence in developing countries. Experimental malnutrition models have been useful to study the effects of malnutrition at early ages. The purpose of this study was to determine if severe malnutrition induced during lactation in rats increases DNA damage in spleen, peripheral blood, and bone marrow cells, as well as in isolated lymphocytes or lymphoid cells from the same tissues. These cells were obtained from malnourished rats at weaning (21 days of age). DNA damage was estimated by using the alkaline single cell electrophoresis assay. The results obtained in this study indicate that malnutrition is associated with a significant increase in DNA damage in all cell types that were studied in malnourished rats. The analysis of the length of DNA migration and dispersion coefficient showed that some cell types were more susceptible to DNA damage related with malnutrition. The damage observed could be due to the deficiency of several essential nutrients required for protein synthesis that are associated with DNA integrity, impaired DNA repair mechanisms, and/or to the unavailability of molecules necessary to protect the cells against DNA oxidative damage. This damage may produce negative effects for the further development of the organism, since bone marrow is the main site of hematopoiesis and spleen is an important lymphopoietic organ. Also, the increased level of DNA damage in peripheral blood lymphocytes and leukocytes could be related to negative effects such as a deficient immune response.