Months Of Refeeding Research Articles

Up-regulation of the kidney renin angiotensin system contributes to long-term renal dysfunction in severe food restricted-refed female rats

Background: Severe food restriction (sFR) due to various psychological, environmental, and economical reasons can have adverse consequences to cardiovascular functioning and health. Less understood are the long-term risks for developing cardiovascular disease after the sFR period has ended. The renin-angiotensin system (RAS) is responsible for regulating blood pressure and we have found that the RAS is chronically upregulated months after the sFR is over and body weight (BW) recovered due to refeeding (sFR-Refed). AIM: Determine the role of the kidney in the chronic up-regulation of the RAS in sFR-Refed rats. Methods: We investigated the long-term consequences of sFR after refeeding on kidney structure and function in sFR-Refed rats. Female Fischer rats (3-months-old) were maintained on normal chow (Ctrl) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received regular chow ad libitum for 3 months. Kidney function was analyzed by precision ultrasound. ACE expression (qPCR) and activity (fluorescent assay) were measured and renal pathology was assessed by H&E staining. Results: After 2 weeks of sFR, rats lost 15% of their initial BW [DFinal/Initial): Ctrl, 1.50±0.80 vs sFR, -15.4±1.1; p<0.001; n=8]. After 3 months of refeeding, there was no detectable difference in BW, blood pressure and heart rate between Ctrl and sFR-Refed groups. However, the renal artery blood flow was reduced by 13% [(mm/s): Ctrl, 255 ± 12 vs sFR-Refed, 199 ± 7.8; p<0.02; n=4-8 Glomeruli size was reduced [(mm): Ctrl, 399 ± 6.2 vs sFR-Refed, 383 ± 3.8; p<0.05; n=9] and renal AT1R mRNA expression was increased by 1.3-fold [(fold of Ctrl): Ctrl, 1.00 ± 0.060 vs sFR-Refed, 1.29 ± 0.040; p<0.005; n=8]. Conclusion: In summary, AT1Rs in the renal cortex are up-regulated under conditions in which kidney structure and function are impaired months after the sFR period has ended and BW is restored to normal levels. These findings suggest increased renal AT1R activity contributes to the long-term renal dysfunction observed in sFR-Refed rats. Further research is needed to understand how women who are subjected either voluntarily (e.g., crash diets) or involuntarily (e.g., very low food security) to periods of inadequate caloric intake could be at increased risk for developing renal disease later in life. AHA: 940246 (AS); IH 1R01HL119380 (KS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

EFFECT OF SEVERE FOOD RESTRICTION ON BLOOD PRESSURE REGULATION IN THE FEMALE SPRAGUE DAWLEY RAT

Objective: Eating disorders have both short term and long term consequences that can be present years after recovery. However, the molecular mechanisms contributing to the increased cardiovascular risk for “recovered’’ individuals is still largely unknown. We have previously found that inbred female F344 rats have altered renin-angiotensin-aldosterone-system regulation of mean arterial blood pressure(MAP) following a 60% food restriction (to achieve a 15–20% body weight drop in F344). The purpose of this work was to see if these are robust changes that can be replicated in an outbred strain which is a better model of the human population. Design and method: Two-month-old female Sprague Dawley(SD) rats were divided into control(CON) that had access to food ad libitum and a food restricted(FR) that received a 56% food restriction (to achieve a 15–20% body weight drop in SD). After 2 weeks, CON (n = 5) and FR (n = 5) rats were sacrificed, the remaining FR (n = 4) and CON (n = 4) rats received chow ad libitum for 5 months. Prior to sacrifice, an acute MAP response to 200ng/kg Angiotensin II(ANGII) was recorded from the femoral artery under anesthesia by indwelling catheter. Results: We found that after 14 days of food restriction the FR rats had lower baseline MAP compared to CON rats (CON = 92 ± 3.0 vs. FR = 75 ± 0.4mmHG, p < 0.05), however, both groups had the same absolute response in MAP to ANGII infusion (CON = 19 ± 2.8 vs. FR = 18 ± 2.0 mmHG). After 5 months of refeeding we found that there were no statistical differences in baseline MAP between the groups (CON = 86 ± 2.2 vs. FR = 91 ± 4.8mmHg), however, there was a trend towards an increase in peak MAP response to ANGII (CON = 19 ± 1.5 vs. FR = 27 ± 3.0mmHg, p = 0.056). Conclusions: When compared to F344, we found similar trends in baseline MAP immediately following food restriction and months after refeeding. We did not detect a blunting of the ANGII response immediately following food restriction as in F344. We did find similarities between F344 and SD in response to ANGII months after refeeding. Food restriction appears to create a robust change in the response to ANGII months after refeeding, that is not strain specific.

Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

A Novel 7-Days Prolonged Dietary Deprivation Regimen Improves ALT and UA After 3-6 Months Refeeding, Indicating Therapeutic Potential.

Objectives: The aim of this study was to evaluate a total fasting regimen assisted by a novel prebiotic, Flexible Abrosia (FA), in more than 7 days of continual dietary deprivation (7D-CDD). Our analysis included basic physical examinations, bioelectrical impedance analysis, and clinical lab and ELISA analysis in normal volunteers.Methods: Seven healthy subjects with normal body weight participated in 7D-CDD with the assistance of a specially designed probiotic. Individuals were assigned to take FA (113.4 KJ/10 g) at each mealtime to avoid possible injuries to intestinal flora and smooth the hunger sensation. During 7D-CDD, the subjects were advised to avoid any food intake, especially carbohydrates, except for drinking plentiful amounts of water. The examination samples were collected before CDD as self-control, at 7 days fasting, and after 7~14 days of refeeding. Three subjects were also tested after 6-m refeeding.Results: The FA-CDD regimen significantly decreased suffering from starvation, with tolerable hunger sensations during the treatment. With the addition of daily mineral electrolytes, the subjects not only passed through the entire 7D-CDD regimen but also succeed in 12~13 days total fasting in two subjects. There was a significant reduction in blood glucose, insulin, and high-density lipoprotein levels during fasting, and the blood concentrations of uric acid (UA), alanine aminotransferase (ALT), and creatine kinase (CK) were increased. However, after more than 2 months of refeeding, the disease markers ALT, GOT, and CK either remained stable or were slightly downregulated compared to their initial D0 control level.Conclusion: Our experiment has supplied the first positive evidence that, with the assistance of a daily nutritional supply of around 100 kcal total calories to their intestinal flora, human subjects were able to tolerate hunger sensations. We have found that, although 7D-CDD induced increases in UA, CK, and transferases during fasting, refeeding led the markers to become either down-regulated or unchanged compared to their initial levels. This phenomenon was further confirmed in longer-term (6 m) recovery. Our results failed to support the hypothesis that fasting induced liver damage, since ALT, GOT, and CK remained low after longer-term refeeding. Our findings indicate that the 7D-CDD regimen might be practical and that it might be valuable to design larger clinical fasting trials for improvement of health strategy-targeting in metabolic disorders.

Long‐term consequences of severe food restriction on the heart of female Fischer rats

IntroductionIndividuals under voluntary (e.g., anorexia, crash diets) or involuntary (e.g., very low food security) severe food restriction (sFR) are at increased risk for developing cardiovascular disease during the sFR period and also long term well after the sFR period has ended. During the sFR period patients present long QT interval, arrhythmia, hypotension and bradycardia and sometimes death, which is primarily due to heart failure. Unfortunately, Little is known, however, almost nothing is known about the heart function when these individuals recoveries the body weight. Cardiovascular disease due to earlier exposure to sFR is an underappreciated and understudied problem and there are no Aim: ‐consequencesof sFR on heart structure and function known therapeutic strategies designed to prevent or reverse the increased risk after recovery from the sFR period(s).MethodsFemale Fischer rats with 3‐month‐old were divided in a control (CT) (ad libitum regular chow; n=18) and sFR (60% reduction of daily food intake, n=18) group. After 2 weeks all rats received regular chow ad libitum for 3 months. The control and sFR rats were then divided into three groups each and infused with vehicle (n=8), in a bolus infusion of angiotensin II (400ng/Kg – 0.2mL; n=6), or subjected to ischemia‐reperfusion using a Langendorff preparation (n=4). At the end of the experiment, the rats were sacrificed and the hearts were removed for histology.ResultsAfter 14 of sFR body weight was reduced by 18%, Mean arterial pressure (p=0.03), heart rate (p=0.03) and wet heart weight (p=0.009) were reduced. After 3 mo of refeeding, body weight, MAP, HR, and wet heart weight were indistinguishable from the control animals. Despite normalization of some parameters,, 3 months of refeeding, analysis of H&E stained myocardium tissue in vehicle‐treated rats revealed that parallel orientation of myofiber and clear striations present in normal cardiomyocytes were lost in sFR‐refed animals indicating severe cardiac damage. Uneven blood‐filling of the vessels of the microcirculatory and prominent interstitial edema of the myocardium was observed. The cardiomyocytes were polymorphic and single cardiomyocytes also found to be atrophied. Infusion of angiotensin II to sFR‐refed animals, but not to control animals, resulted in the occurrence of focal necrotic lesions causing by multiple contractures of cardiomyocytes, indicating cardiomyocytes had disrupted of calcium homeostasis and increased calcium sensitivityof sFR‐refed animals. The magnitude of ischemia/reperfusion‐induced damage was also greater in sFR‐refed animals compared to control animals in Langendorff preparations. After ischemia/reperfusion injury, along with deeply eosinophilic myofibers, large amounts of necrotic cardiomyocytes were found in sFR‐refed rats, but not in control.ConclusionDespite normalization of body weight, blood pressure, heart rate and wet heart weight after 3 months of refeeding, the hearts from animals subjected to severe food restriction are severely damaged. These findings suggest individuals who have recovered from prior exposure to a period of sFR are at increased risk of developing cardiovascular disease.Support or Funding InformationNIH 1R01HL119380 (KS)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intermittent Brugada syndrome in an anorexic adolescent girl

We report an anorexic adolescent girl with an intermittent Brugada syndrome. A 14-year-old anorexic girl with a body mass index (BMI) of 13.15kg/m2 was admitted in the acute state of the disease with an ST elevation in V1 and V2, suggestive of Brugada syndrome. After 1 month of re-feeding, a control electrograph (ECG) was normal, but after an 8-month follow-up control with a nearly normal BMI, the ECG was again suggestive of Brugada syndrome. A genetic analysis of the gene SNC5A established a genetic change (p Leu 1582 pro), which provides the final explanation for the Brugada syndrome. Every rhythm problem in the acute state or during the re-feeding procedure deserves a strict follow-up to distinguish iatrogenic from heritable rhythm problems.<Learning objective: (i) We report the first case of a patient with anorexia nervosa with an intermittent Brugada syndrome. (ii) Moderate hypothermia can decrease the depolarization of pacemaker cells and cause ST-segment changes. (iii) Every rhythm problem in the acute state or during the re-feeding procedure deserves a strict follow-up to distinguish iatrogenic from heritable rhythm problems. (iv) A genetic analysis can make the distinction and is necessary to give advice for the future lifestyle of the patient.>

Major urinary protein 5, a scent communication protein, is regulated by dietary restriction and subsequent re-feeding in mice

Major urinary proteins (Mups) are important for rodent scent communication and sexual behaviour. Recent evidence suggests that Mup1 may be regulated by fasting and re-feeding (RF). However, other Mup isoforms are poorly investigated, and data on the impact of long-term dietary restriction (DR) and ad libitum RF on Mup expression are missing. We investigated the effects of long-term 25 per cent DR and subsequent RF on Mup expression in male C57BL6 mice. DR significantly decreased Mup gene expression, hepatic and urinary protein levels compared with ad libitum (AL) fed control mice, with the greatest downregulation found for Mup5 expression. The decline in Mup expression was inverted by six months of RF. Because of inhibitory glucocorticoid response elements in the genomic sequence of the Mup5 gene, the observed inverse correlation of nuclear glucocorticoid receptor levels with Mup expression in response to DR and subsequent RF is a possible regulatory mechanism. Additionally, gene-expression-inhibiting histone deacetylation (H3K9) occurred in the region of the Mup5 gene in response to DR. We assume that Mup may act as a molecular switch linking nutritional status to sexual behaviour of mice, and thereby regulating male fertility and reproduction in response to food supply.

Beneficial effects of a 6-month dietary restriction are time-dependently abolished within 2 weeks or 6 months of refeeding—genome-wide transcriptome analysis in mouse liver

Dietary restriction (DR) has been shown to exert a number of beneficial effects including the prolongation of life span. One of the mechanisms by which DR leads to these advantages seems to be the induction of endogenous antioxidant defense and stress response mechanisms. However, little is known about the persistence of DR benefits after return to an ad libitum diet. In this study, male C57BL/6 mice were fed 75% of a normal diet for 6 months (DR) followed by 6 months of ad libitum refeeding (RF) and compared to a continuously ad libitum fed control group. To study the impact of DR and RF on the liver transcriptome, a global gene expression profile was generated using microarray technology. In comparison, the DR group showed lower body weight, lower triglyceride and cholesterol levels, reduced lipid peroxidation, and a changed hepatic fatty acid pattern. mRNA transcription and activity of antioxidant and phase II enzymes, as well as metallothionein 1 gene expression, were increased and autophagy was induced. Shifting from long-term DR to RF abolished 96% of the DR-mediated changes in differential gene expression within 2 weeks, and after 6 months of refeeding all of the previously differentially expressed genes were similar in both groups. These results indicate that DR has to be maintained continuously to keep its beneficial effects.

Pericardial Effusions in Adolescent Girls With Anorexia Nervosa: Clinical Course and Risk Factors

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8–17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between ≥ 0.35–2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI ≤ 13,5 kg/m², weight loss ≥ 25% and IGF-1-level ≤100 ng/ml. Pericardial effusions are common in adolescent AN patients. They are mostly asymptomatic not requiring any intervention and spontaneously regress with refeeding. They are more common in the patients with the most significant weight loss.

Oxidative stress parameters during starvation and refeeding periods in Adriatic sturgeon (Acipenser naccarii) and rainbow trout (Oncorhynchus mykiss)

This work analyses the changes in the redox balance in two fish species: Adriatic sturgeon (Acipenser naccarii) and rainbow trout (Oncorhynchus mykiss) during starvation and refeeding period. The starvation period raised the lipid peroxidation (thiobarbituric-acid-reacting substances) levels in liver and blood, while a decline occurred in the antioxidant enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) in both fish species. In liver, after the refeeding period, SOD activity recovered in both species, whereas CAT activity recovered only in trout. Furthermore, in both tissues of the two species, the lipid peroxidation levels remained high after 2 months of refeeding. In white muscle and heart, the lipid peroxidation levels indicate that these tissues did not undergo oxidative stress during the 72-day period. During starvation, in the muscle of both fish the fall in the lipid peroxidation level coincided with a rise in CAT, GPX and GR. The refeeding period in this tissue raised the lipid peroxidation level, and the enzymatic activities reached the values of the first point of starvation. In heart, no oxidative damage was detected during starvation in either species. The CAT and SOD activities increased during the starvation period only in trout.

Distinct role of insulin and IGF-I and its receptors in white skeletal muscle during the compensatory growth of gilthead sea bream ( Sparus aurata)

In order to examine compensatory growth (CG) in gilthead sea bream ( Sparus aurata), we used an experimental protocol involving 1-, 3- or 4-week fasting followed by a one- or two-month re-feeding period. After one month of re-feeding, final body weight gain and growth acceleration in groups fasted for 1 or 3 weeks (W1 and W3) were comparable to the control group values (C), indicating that partial CG was achieved. Fasting had a marked effect on depressing circulating glucose plasma levels, which were recovered to C group values after one month re-feeding. Glycogen content in liver and muscle decreased during fasting and was completely recovered after two month re-feeding. FFA plasma levels increased during fasting trial for all the different experimental groups, whereas lipid content in liver and muscle was depressed, indicating that lipid depot utilization contributes to the energy metabolism of gilthead sea bream. After re-feeding for 1 or 2 months, FFA and lipid content in liver and muscle were comparable to C group values. Plasma insulin and IGF-I values decreased during the fasting trial, while normal levels were restored after 1 month of re-feeding IGF-I and insulin binding assays in semi-purifications of soluble proteins from white skeletal muscle showed that IGF-I binding increased with fasting while insulin binding decreased. However, the specific binding for these two peptides was comparable to C group values after re-feeding for 1 or 2 months. In conclusion, after re-feeding insulin and IGF-I recovery was parallel with increases in weight gain and growth acceleration in those groups which showed diminutions in growth during the period of food restriction. Furthermore, the differential regulation of the specific binding for insulin and IGF-I in white skeletal muscle during fasting, indicates that these two receptors play distinct roles in response to the nutritional status of the animal.

Modulation of Adiponectin and Leptin during Refeeding of Female Anorexia Nervosa Patients

Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T(4) or cortisol levels. Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.

Modifications of erythrocyte membrane fluidity from patients with anorexia nervosa before and after refeeding

Erythrocyte membrane characteristics were compared in 15 normal women and 15 women with anorexia nervosa; the patients were studied at hospital admission and again after 1 month of refeeding. At admission, physical properties of erythrocyte membranes, studied with electron spin resonance spectrometry, significantly differed between the anorexic patients and the normal volunteers. Fluidity from the hydrophobic part of the erythrocyte membrane, estimated by the correlation frequency, was decreased in the patients. After 1 month of refeeding, fluidity increased. One of the possible mechanisms of the variation of membrane fluidity could be the effect of cholesterol on membrane structure. Increased cholesterol levels in anorexic subjects could reduce fluidity. These alterations in membrane fluidity could explain some of the neurobiological abnormalities observed in anorexia nervosa.

Changes in body composition during refeeding of patients with anorexia nervosa

Changes in body composition were studied in 13 girls with anorexia nervosa before and during 2 months of refeeding. Fat body mass and fat-free body mass were derived from skin-fold measurements. Total body potassium was measured by whole body counter, and intracellular water was calculated from it. Extracellular water was measured as the bromide space after oral bromide administration. A gradual increase was noted in weight, fat body mass, fat-free body mass, and total body potassium during refeeding. Extracellular water was expanded on admission and increased in all patients in the first weeks of treatment; later it fell to normal. Most of the changes in fat-free body mass over the first weeks of refeeding could be accounted for by an expansion in extracellular water. Particular care must therefore be taken with fluid balance during the first few weeks of refeeding.

Interaction between pre-weaning undernutrition and post-weaning environmental enrichment on somatic development and behaviour in male and female rats

Male and female rats were undernourished from birth to 30 days by restricting access to the lactating mother, and then fed ad libitum. At weaning, underfed and normally suckled controls were permanently housed either in pairs in standard cages or in groups of 10 in 1 m 3 cages containing ladders, ropes etc. Severe undernutrition during suckling followed by 4 months of refeeding, produced some changes in sexual behaviour in adult males (increased ejaculation frequency) but had no effect on behaviour in open field, dark preference or passive avoidance. Differential post-weaning environment produced significant differences in behaviour, irrespective of previous feeding conditions. Enriched animals were more active and exploratory. Females differed from males in the same direction as enriched from standard, and were more responsive to social and housing conditions.

The Regulation of Erythropoiesis in Protein‐Energy‐Malnutrition

The erythropoietin (ESF) content of plasma and urine has been studied in children with protein-energy-malnutrition (PEM) living in the Kivu province at an altitude of 1467--2000 m. On admission, packed cell volume (PCV) was moderately reduced; after 2 months of refeeding PCV had increased but was still lower than in the controls. Plasma ESF was increased on admission and in patients refed for 2 months. The expected positive correlation between serum and urine ESF levels was found after refeeding but not on admission; the last finding could not be explained by the presence of erythropoiesis inhibiting factor(s) in the urine. In spite of the normal 2,3-DPG and P50 previously described in PEM in Kivu, the anaemia associated with this disease is not merely an adaptation to lowered oxygen consumption and there must be some disturbances in the responsiveness of bone marrow to ESF. The high ESF values observed after 2 months of refeeding confirm that the restoration of the red cell volume proceeds slowly.

Effects of early protein-calorie malnutrition on the immune response.

Intrauterine and early postnatal malnutrition caused a marked and protracted weight reduction of the body, spleen, and thymus. The mean body weight of the offspring of the malnourished mothers at weaning was 25 +/- 10 g whereas that of the controls was 75 +/- 20 g. At weaning the mean spleen weight of the malnourished offspring was 0.19 +/- 0.05 g and that of their controls was 0.4 +/- 0.13 g. During refeeding the spleen weight but not the thymus weight of the malnourished offspring caught up with that of the controls after about 70 days. After refeeding for as long as 4 months the thymus weight of the malnourished was still significantly (P less than 0.01) less than that of the corresponding weight-matched controls. Primary and secondary plaque-forming cells (PFC) in both the spleen and thymus of the weanling malnourished offspring were barely detectable whereas spleen of their controls had mean approximate values of 50 x 10(3) primary PFC and 70 x 10(3) secondary PFC. The corresponding values in the control thymus were 20 x 10(2) primary PFC and 8 x 10(2) secondary PFC. After refeeding for 4 months of the weanling malnourished offspring their primary and secondary PFC in the spleen increased to about one-half the level of that in their controls whereas the PFC in the thymus were still barely detectable. On the other hand, mean primary and secondary rosette-forming cells (RFC) in the spleen of the weanling malnourished offspring were less than 1 x 10(3) in comparison to the 80-90 x 10(3) in the controls (P less than 0.001). In the thymus too, mean primary and secondary RFC were also less than 1 x 10(3), whereas the corresponding figure in the controls was 30-50 x 10(3) RFC. After refeeding for 4 months the mean values of both the primary and secondary RFC in the spleen and thymus continued to remain less than 1 x 10(3). Although cell morphology in the spleen of the malnourished offspring had returned to normal appearance after 4 months of refeeding, that of the corresponding thymus had not done so completely. For instance, thymic corticomedullary function had reappeared by this time but thymocytes were still less in number than in the controls. By the 8th postnatal day serum IgG2b allotype became detectable in the control offspring, but it was not until day 20 that this IgG allotype could be detected in the malnourished offspring. IgG2a allotype could be detected in the sera of both the malnourished and control offspring.

Serial measurements of vitamin B-12 and vitamin B-12-binding capacity in marasmic kwashiorkor

Vitamin B-12 and total vitamin B-12-binding capacity (TBBC) have been determined by a radio-saturation assay in the blood of a large group of patients suffering from marasmic kwashiorkor on admission, and during their whole re-feeding. The results have been compared with values obtained in control children of the same ethnic group and with normal children living in Belgium. Vitamin B-12 levels are high on admission and only normalize during the second month of re-feeding. TBBC is normal on admission but significantly increases during re-feeding.

Synthesis and Degradation of Mixed Proteins, and Composition Changes in Skeletal Muscle of Malnourished and Refed Rats

Selected compositional parameters of hind leg skeletal muscle and the rates of synthesis and degradation of mixed proteins were measured in rats (154 g initial weight) after ad libitum feeding a low protein diet for 17 weeks, and after 2 to 9 days and 59 to 66 days of refeeding with an adequate diet. The half-life for degradation of the mixed muscle proteins was determined from the change in total hind leg radioactivity between 2 and 7 days following an intravenous injection of 4-MC-aspartic acid. From these data and the size of the hind leg muscle protein pool, the rate of muscle protein synthesis was calcu lated. The prolonged protein-depletion phase resulted in loss of body weight, in crease in the water, chloride and DNA concentrations and a decrease in lipid and RNA in muscle. Refeeding rapidly reversed these changes. The half-life for catabolism of mixed proteins in muscle of depleted rats was 10.2 days as com pared (P > 0.1) with a value of 13.1 days for well-nourished weight-control rats (74 g). During the first 9 days of refeeding, the synthesis of mixed muscle pro teins proceeded at a greater rate (P < 0.01) than in the weight control rats. In contrast, the catabolism of muscle protein was abolished during this period. After 2 months of refeeding, the half-life for catabolism of mixed muscle proteins was 12.6 days. It is concluded that increased synthesis and decreased catabolism of protein play major roles in bringing about a rapid accumulation of muscle pro tein during early protein refeeding. J. Nutr. 101: 1379-1390, 1971.