Nutritional Growth Retardation Research Articles

Air pollution induces morpho-functional, biochemical and biomechanical vascular dysfunction in undernourished rats

Air pollution (gases and particulate matter -PM) and child undernutrition are globally recognized stressors with significant consequences. PM and its components breach the respiratory alveolar-capillary barrier, entering the vasculature transporting not only harmful particles and its mediators but, altering vascular paracrine and autocrine functions.The aim of this study was to investigate the effects of Residual Oil Fly Ash (ROFA), on the vasculature of young animals with nutritional growth retardation (NGR). Weanling rats were fed a diet restricted 20% (NGR) compared to ad libitum intake (control-C) for 4 weeks. Rats were intranasally instilled with 1 mg/kg BW of ROFA. After 24h exposure, histological and immunohistochemical, biochemical and contractile response to NA/ACh were evaluated in aortas.ROFA induced changes in the tunica media of the aorta in all groups regarding thickness, muscular cells and expression of Connexin-43. ROFA increased TGF-β1 and decreased eNOs levels and calcium channels in C and NGR animals. An increment in cytokines IL-6 and IL-10 was observed in C, with no changes in NGR. ROFA exposure altered the vascular contractile capacity.In conclusion, ROFA exposure could increase the risk for CVD through the alteration of vascular biochemical parameters, a possible step of the endothelial dysfunction.

Decreased immune response in undernourished rats after air pollution exposure

Children are highly vulnerable subpopulation to malnutrition and air pollution. We investigate, in a rat nutritional growth retardation (NGR) model, the impact of Residual Oil Fly Ash (ROFA) on the lung immune response using in vitro and ex vivo methods. In vitro: Alveolar macrophages (AM) were isolated from Control (C) and NGR animals, cultured and treated with ROFA (1–100 µg/ml) for 24 h. Ex vivo: C and NGR rats were intranasally instilled with ROFA (1 mg/kg BW) or PBS. 24 h post-exposure AM were isolated and cultured. ROFA-treatment increased superoxide anion production and TNFα secretion in C-AM in vitro, though for NGR-AM this response was lower. A similar pattern was observed for TNFα and IL-6 secretion in ex vivo experiments. Regarding the antioxidant response, although NGR-AM showed increased Nrf2, after ROFA instillation an attenuated activation was observed. To conclude, chronic undernutrition altered AM response to ROFA affecting immune responsiveness to air pollutants.

Effect of anthelmintic treatment on serum free IGF-1 and IGFBP-3: a cluster-randomized-controlled trial in Indonesia

In children, soil-transmitted helminth infections have been linked to poor nutritional status and growth retardation in association with lower levels of IGF-1. In adults, IGF-1 has an anabolic and metabolic function and is related to nutritional status. Here, we assessed the impact of helminth infection on free IGF-1 and its major binding protein, IGFBP-3, in adults. The levels of IGF-1 and IGFBP3 were measured in 1669 subjects aged ≥ 16 years, before and after receiving four rounds of albendazole 400 mg/day or matching placebo for three consecutive days. Helminth infection status was assessed by microscopy (Kato-Katz) and PCR. Serum free IGF-1 level was significantly lower in helminth-infected subjects [mean difference and 95% CI − 0.068 (− 0.103; − 0.033), P < 0.001 after adjustment for age, sex, body mass index, and fasting insulin level]. There was no difference in IGFBP-3 level between helminth infected versus non-infected subjects. In the whole study population, albendazole treatment significantly increased serum free IGF-1 level [estimate and 95% CI 0.031 (0.004; − 0.057), P = 0.024] whereas no effect was found on the IGFBP-3 level. Our study showed that helminth infection in adults is associated with lower free IGF-1 levels but not with IGFBP-3 and albendazole treatment significantly increases free IGF-1 levels in the study population.Clinical Trial Registration: https://www.isrctn.com/ISRCTN75636394.

Dietary Complex and Slow Digestive Carbohydrates Prevent Fat Deposits During Catch-Up Growth in Rats.

A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early caloric restriction: an increase in adiposity combined with poorer muscle performance, insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in myocyte enhancer factor 2D (MEF2D) and creatine kinase as markers of muscle differentiation as well as better insulin sensitivity, enhanced glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted glycogen storage and decreased fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as obesity, insulin resistance, dyslipidemia, and liver fat deposits later in life.

Oxidative stress response to air particle pollution in a rat nutritional growth retardation model

ABSTRACTAir pollution consisting of gases and particulate matter-(PM) represents a health problem in cities worldwide. However, air pollution does not impact equally all individuals, as children appear to be more vulnerable subpopulations. Air pollution and malnutrition are two distinct factors that have been associated with oxidative damage. Therefore, the interaction between environmental exposure and nutritional status in populations at risk needs to be explored. The aim of this study was to examine oxidative metabolism in lung, heart and liver in malnourished young rats exposed to residual oil fly ash (ROFA). A Nutritional Growth Retardation (NGR) model was developed in weanling male rats placed on a 20% restricted balanced diet for 4 weeks. Then, NGR and control rats were intranasally instilled with either ROFA (1mg/kg BW) or phosphate buffered saline (PBS). Twenty-four hr post-exposure lung, heart and liver were excised, and serum collected. ROFA induced lung and liver inflammation in control and NGR animals as evidenced by lung polymorphonuclear neutrophil (PMN) recruitment and alveolar space reduction accompanied by liver lymphocyte and binucleated hepatocyte level increase. In lung and liver, antioxidant defense mechanisms reduced lipoperoxidation. In contrast, only in NGR animals did ROFA exposure alter heart oxidative metabolism leading to lipid peroxidation. Although histological and biochemical tissue alterations were detected, no marked changes in serum liver and heart systemic biomarkers were observed. In conclusion, NGR animals responded differently to PM exposure than controls suggesting that nutritional status plays a key role in responsiveness to ambient air contaminants.

Mechanical mandible competence in rats with nutritional growth retardation

ObjectiveIn order to provide a better understanding of the sympathetic nervous system as a negative regulator of bone status, the aim of the study was to establish the biomechanical mandible response to different doses of a β-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. MethodsRats were assigned to eight groups: Control (C), C+P3.5 (CP3.5), C+P7 (CP7), C+P14 (CP14), NGR, NGR+P3.5 (NGRP3.5), NGR+P7 (NGRP7) and NGR+P14 (NGRP14). C, CP3.5, CP7 and CP14 rats were freely fed with the standard diet. NGR, NGRP3.5, NGRP7 and NGRP14 rats received, for 4 weeks (W4), 80% of the amount of controls food consumed. Propranolol 3.5, 7 and 14mg/kg/day was injected ip 5days per week in CP3.5 and NGRP3.5, CP7 and NGRP7, CP14 and NGRP14, respectively. At W4, zoometry, mandible morphometry, static histomorphometric and biomechanical competence were performed. ResultsA dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. ConclusionThese findings evidenced that sympathetic nervous system activity is a negative regulator of mandible mechanical competence in the nutritional growth retardation model. Propranolol 7mg/kg/day, under the regimen usage, seems to be appropriate to blockade SNS activity on mandible mechanical performance in NGR rats, probably associated to an effect on bone mechanostat system ability to detect disuse mode as an error.

Liraglutide prevents fast weight gain and β-cell dysfunction in male catch-up growth rats.

We reported recently that after a nutritional growth retardation, rats showed significant weight gain, central fat accumulation, dyslipidemia, and β-cell dysfunction during a catch-up growth (CUG) phase. Here, we investigated whether glucagon-like peptide-1 (GLP-1) ameliorated the rapid weight gain, central fat deposition, and β-cell dysfunction during the CUG in rats. Sixty-four male Sprague Dawley rats were stratified into four groups including normal control group, CUG group, catch-up growth with liraglutide treatment group, and catch-up growth with liraglutide and exendin 9-39 treatment group. Energy intake, body weight, and body length were monitored. Fat mass percentage was analyzed by dual energy X-ray absorptiometry scan. Plasma triglyceride and non-esterified fatty acid were measured. The β-cell mass was analyzed by morphometric analysis and signaling molecules were examined by Western blot and real-time PCR. Insulin secretion capability was evaluated by hyperglycemic clamp test. Liraglutide prevented weight gain and improved lipid and glucose metabolism in rats under CUG conditions, which were associated with reduced fasting insulin levels and improved glucose-stimulated insulin secretion. Improved β-cell function is found to be associated with increased β-cell replication as determined by β-cell density and insulin-Ki67 dual staining. Furthermore, liraglutide increased islet pancreatic duodenal homeobox-1 (Pdx-1) and B-cell lymphoma-2 transcript and protein expression, and reduced Procaspase-3 transcript and Caspase-3 p11 subunit protein expression, suggesting that expression of Pdx-1 and reduction of apoptosis may be the mechanisms involved. The therapeutic effects were attenuated in rats co-administered with exendin 9-39, suggesting a GLP-1 receptor-dependent mechanism. These studies revealed that incretin therapy effectively prevented fast weight gain and β-cell dysfunction in rats under conditions of nutrition restriction followed by nutrition excess, which is in part due to enhanced functional β-cell mass and insulin secretory capacity.

MRNA of cytokines in bone marrow and bone biomarkers in response to propranolol in a nutritional growth retardation model

BackgroundThe aim of this study was to assess mRNA of IL-6, TNFα and IL-10 cytokines in bone marrow, possible mediators involved in altered bone remodeling with detrimental consequences on bone quality in NGR (Nutritional growth retardation) rats. MethodsWeanling male Wistar rats were assigned either to control (C) or experimental group (NGR) (n=20 each). C and NGR groups were assigned to 2 groups according to receiving saline solution (SS) or propranolol hydrochloride (P): C, C+P (CP), NGR or NGR+P (NGRP). For 4 weeks, NGR and NGRP rats received 80% of the amount of food consumed by C and CP, respectively, the previous day, corrected by body weight. P (7mg/kg/day) was injected ip 5 days/week, for 4 weeks in CP and NGRP rats. Body weight and length were recorded. After 4 weeks, blood was drawn. Femurs were dissected for RNA isolation from bone marrow and mRNA of cytokines assays. ResultsFood restriction induced a significant negative effect on body growth in NGR and NGRP rats (p<0.001). P had no effects on zoometric parameters (p>0.05). CTX-I increased in NGR rats vs. C (p<0.001), but diminished in NGRP (p<0.01). Serum osteocalcin, PTH, calcium and phosphate levels remained unchanged between groups (p>0.05). In NGR, bone marrow IL-6 mRNA and IL-10 mRNA levels were low as compared to other groups (p<0.05). In contrast, bone marrow TNF-α mRNA levels were significantly high (p<0.05). ConclusionsThis study provides evidences that NGR outcomes in a bone marrow proinflammatory microenvironment leading to unbalanced bone remodeling by enhancement of bone resorption reverted by propranolol.

Oesophagogastric reconnection is possible

The first oesophagogastric dissociation was described by Bianchi in 1997 for the treatment of severe gastro-oesophageal reflux (GOR) in neurological patients to avoid serious respiratory complications. The dissociation leads to malabsorption and growth problems. We describe the first two cases of oesophagogastric reconnection long after lung growth. Case no. 1 was a 12.7-year-old child with a history of type I oesophageal atresia. He required oesophagocoloplasty and gastric dissociation by the Bianchi procedure at the age of 3months. He has oesophagogastric reconnection at 11years old because he had a several macrocytic anaemia. Case no. 2 was also a 12-year-old boy, with an unlabelled multiple malformation syndrome with type I oesophageal atresia. He had an oesophagocoloplasty with gastric dissociation at the age of 3months to protect his lungs. The reconnection was proposed at 10years old because he developed multiple nutritional deficiencies and growth retardation. The two cases have no clinical symptom of reflux and their post-operative digestive contrasts are normal. Reconnection appears possible with or without preserving the Roux-en-Y loop. It improves absorption and corrects any vitamin deficiencies, allows the reconnected stomach to be monitored in terms of reflux and malignancy and enables enteral nutrition supplementation to be stopped. The possibility of reconnection after the Bianchi procedure therefore extends its indications, mostly in the case of oesophageal atresia complicated by severe GOR with pulmonary repercussions or tracheoesophageal cleft.

Dyslipidemia is not associated with cardiovascular disease risk in an animal model of mild chronic suboptimal nutrition

Previous studies performed in an experimental model of nutritional growth retardation (NGR) have observed metabolic adaptation. We hypothesized that changes in lipid-lipoprotein profile, glucose, and insulin levels occur, whereas overall body growth is reduced.The aim of this study was to assess serum lipid-lipoprotein profile, hepatogram, insulinemia and glycemia, and CVD risk markers in rats fed a suboptimal diet. Weanling male rats were assigned either to control (C) or NGR group. In this 4-week study, C rats were fed ad libitum a standard diet, and NGR rats received 80% of the amount of food consumed by C. Zoometric parameters, body fat content, serum lipid-lipoprotein profile, hepatogram, insulinemia, and glycemia were determined, and the cardiovascular disease (CVD) risk markers homeostasis model assessment-insulin resistance and homeostasis model assessment and β-cell function were calculated. Suboptimal food intake induced a significant decrease in body weight and length, which were accompanied by a reduction of 50% in body fat mass. Serum lipoproteins were significantly higher in NGR rats, with the exception of high-density lipoprotein cholesterol, which remained unchanged. Nutritional growth retardation rats had decreased triglycerides compared with C rats. No significant differences were detected in liver function parameters. The CVD risk markers homeostasis model assessment (HOMA)-insulin resistance and homeostasis model assessment and β-cell function were significantly lower in NGR rats. Mild chronic suboptimal nutrition in weanling male rats led to growth retardation and changes in the lipid-lipoprotein profile, glucose, and insulin levels while preserving the integrity of liver function. These data suggest a metabolic adaptation during suboptimal food intake, which ensures substrates flux to tissues that require constant energy-in detriment to body growth. The CVD risk markers suggested that mild chronic food restriction of approximately 20% could provide protection against this degenerative disease.

Nutrition and Growth - Review

Nutrition plays a fundamental role in determining the growth of individuals. An appropriate growth progression is considered a harbinger of adequate nutrient intake and good health. On the other hand growth deceleration with or without short stature may indicate inadequate nutrition, even when there is no body weight deficit for height. Nutritional growth retardation (NGR) is most prevalent in populations at risk of poverty. However in affluent communities patients with NGR are often referred to the specialist because of short stature and delayed sexual development. The diagnosis may be overlooked and/or be established after exhaustive evaluations, if the pattern of weight progression over time is not considered. Patients with so-called idiopathic short stature may present diminished nutrient intake and decreased IGF-I levels, however their nutritional status and body weight progression patterns are usually not addressed by pediatric endocrinologists. NGR patients may cease to gain appropriate weight and fail to grow in height, even without exhibiting body weight deficits for height. They adapt to decreased nutrient intake by decreasing growth progression and thereby achieve equilibrium by decreasing the nutrient demands. This occurs by diminishing their metabolic rates and erythrocyte Na+, K+- ATPase activity, however they may not present alterations in other clinical biochemical markers of malnutrition. Therefore accurate weights and heights plotted on the growth chart over time are necessary to detect NGR. Nutritional rehabilitation is accompanied with catch up growth, though it may be difficult to change the dietary habits of adolescents who exhibit NGR.Conflict of interest:None declared.

Effects of a non-selective beta-blocker on mandibular bone in an animal model of nutritional growth retardation

Effects of a non-selective beta-blocker on mandibular bone in an animal model of nutritional growth retardation

Improved bone status by the β-blocker propranolol in an animal model of nutritional growth retardation

The aim of the present research was to study if the beta-blocker propranolol, which is known to increase bone mass, could reverse the adverse skeletal effects of mild chronic food restriction in weanling rats. Male Wistar rats were divided into four groups: control, control+propranolol (CP), nutritional growth retardation (NGR) and nutritional growth retardation+propranolol (NGRP). Control and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80 % of the amount of food consumed by the control and CP rats, respectively. Results were expressed as mean values and sem. Food restriction induced detrimental effects on body and femur weight and length (P < 0.05) and bone structural and geometrical properties (P < 0.001), confirming results previously shown in our laboratory. However, the beta-blocker overcame the deleterious effect of nutritional stress on load-bearing capacity, yielding load, bone stiffness, cross-sectional cortical bone area and second moment of inertia of the cross-section in relation to the horizontal axis without affecting anthropometric, histomorphometric and bone morphometric parameters. The results suggest that propranolol administration to mildly chronically undernourished rats markedly attenuates the impaired bone status in this animal model of growth retardation.

Decreased energy expenditure—an adaptive mechanism of nutritional growth retardation

The purpose of this prospective study was to evaluate the energy expenditures (EE) and substrate oxidation adaptive mechanisms of patients with nutritional growth retardation (NGR). Healthy children with familial short stature with or without constitutional growth delay (F/CSS) were considered as the control group. Inappropriate growth patterns and decreased erythrocyte Na +K +-ATPase activity were determined for the diagnosis of NGR (NGR = 0.31 ± 0.13 [n = 19] vs F/CSS = 0.49 ± 0.13 [n = 18] units/mg protein; P < .001). A diminished EE (related to expected body weight, NGR = 0.927 ± 0.311 vs F/CSS = 0.998 ± 0.017 [ P < .03]; related to per kilogram per day, NGR = 147.1 ± 31.3 vs F/CSS = 175.5 ± 34.0 kJ kg −1 d −1 [ P < .01]) was observed in the NGR population. A markedly increased carbohydrate (CHO) oxidation rate and a significantly decreased fat oxidation rate (CHO%, NGR = 63.3 ± 4.6 vs F/CSS = 46.1 ± 6.9 [ P < .05]; FAT%, NGR = 15.1 ± 5.4 vs F/CSS = 35.9 ± 11.9 [ P < .05]) with a nonprotein respiratory quotient (NGR = 1.01 ± 0.04 vs F/CSS = 0.89 ± 0.03 [ P < .05]) were detected. The decreased EE of NGR children appears to be an adaptation to decreased energy intake.

Improving Subspecialty Healthcare: Lessons from Cystic Fibrosis

Improving Subspecialty Healthcare: Lessons from Cystic Fibrosis

A Boy with Nutritional Growth Retardation due to Achalasia

A 6-yr-old boy was seen at our hospital due to short stature (-2.0 SD) and frequent vomiting. Peak GH response to arginine and insulin was >10 ng/ml at 10.5 yr of age. Growth retardation was progressive. At 12 yr of age, he was still in prepubertal status with a bone age of 8. His height and body weight were 121.6 cm (-3.57 SD) and 19.0 kg (-2.05 SD). Serum level of IGF-1 was low (35 ng/ml), with marginal hypothyroidism due to non-thyroidal illness (T3 0.93 ng/ml, T4 6.7 μg/dl and TSH 0.08 μU/ml). Serum levels of prealbumin and retinol binding protein were also decreased. Achalasia was diagnosed by esophagography. At the age of 12 yr and 6 mo he underwent laparoscopic extramucosal myectomy with fundoplication, and subsequently his nutritional status improved dramatically. At 15.5 yr old, he had gained height and body weight, 153.2 cm (-2.61 SD) and 38.9 kg (-1.95 SD), respectively, and sexual development had advanced too. The clinical course of this boy revealed that achalasia should be added to the list of causes of nutritional growth retardation in children.

Abnormal glucose tolerance in cystic fibrosis: Why should patients be screened?

Abnormal glucose tolerance in cystic fibrosis: Why should patients be screened?

Achieving genetic potential for nutrition and growth in cystic fibrosis

Achieving genetic potential for nutrition and growth in cystic fibrosis

Total body potassium in cystic fibrosis.

To further evaluate the nature of malnutrition, define at-risk groups, and confirm the efficacy of nutritional supplementation on body composition in cystic fibrosis (CF), we have conducted longitudinal and cross-sectional studies of total body potassium (TBK) in 161 unselected CF subjects aged 1 month to 17 years. TBK was determined by measurement of 40K in a whole body counter, reflecting body cell mass (BCM), the vital work-performing and growing cellular component of the body. Compared with normal TBK data for age and sex from pooled measurements of 1,629 healthy children aged 1 week to 17 years, CF infants (n = 12) diagnosed by newborn screening were depleted in TBK at diagnosis and showed catch-up with therapy by 1 year; CF children aged 2-17 years (n = 140) showed a tendency for inadequate accretion of TBK (and thus BCM) with increasing age, although the normal correlation between TBK and weight and height was maintained in the majority suggesting a pattern of nutritional stunting of growth; and malnourished CF children (n = 9) showed significant catch-up in TBK with long-term nutritional rehabilitation (85-98% of TBK predicted for weight and height). These studies suggest that potentially serious, but possibly correctable deficits, in the growth of the body cell mass as measured by TBK occur commonly in CF. These deficits may be established very early in life and if not corrected lead to progressive nutritional growth retardation with increasing age.

Total Body Potassium in Cystic Fibrosis

To further evaluate the nature of malnutrition, define at‐risk groups, and confirm the efficacy of nutritional supplementation on body composition in cystic fibrosis (CF), we have conducted longitudinal and cross‐sectional studies of total body potassium (TBK) in 161 unselected CF subjects aged 1 month to 17 years. TBK was determined by measurement of 40K in a whole body counter, reflecting body cell mass (BCM), the vital work‐performing and growing cellular component of the body. Compared with normal TBK data for age and sex from pooled measurements of 1,629 healthy children aged 1 week to 17 years, CF infants (n = 12) diagnosed by newborn screening were depleted in TBK at diagnosis and showed catch‐up with therapy by 1 year; CF children aged 2–17 years (n = 140) showed a tendency for inadequate accretion of TBK (and thus BCM) with increasing age, although the normal correlation between TBK and weight and height was maintained in the majority suggesting a pattern of nutritional stunting of growth; and malnourished CF children (n = 9) showed significant catchup in TBK with long‐term nutritional rehabilitation (85–98% of TBK predicted for weight and height). These studies suggest that potentially serious, but possibly correctable deficits, in the growth of the body cell mass as measured by TBK occur commonly in CF. These deficits may be established very early in life and if not corrected lead to progressive nutritional growth retardation with increasing age.