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-ß1 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.

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

Air 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.

OBJECTIVE: In 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 ß-adrenergic antagonist such as propranolol (P) in a stress-induced food restriction model of growth retardation. METHODS: Rats 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. RESULTS: A dose of Propranolol 7mg/kg/day induced interradicular bone volume accretion reaching a mandible stiffness according to chronological age. CONCLUSION: These 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.

Efficacy of phytosterols and fish-oil supplemented high-oleic-sunflower oil rich diets in hypercholesterolemic growing rats.

Phytosterols (P) and fish-oil (F) efficacy on high-oleic-sunflower oil (HOSO) diets were assessed in hypercholesterolemic growing rats. Controls (C) received a standard diet for 8 weeks; experimental rats were fed an atherogenic diet (AT) for 3 weeks, thereafter were divided into four groups fed for 5 weeks a monounsaturated fatty acid diet (MUFA) containing either: extra virgin olive oil (OO), HOSO or HOSO supplemented with P or F. The diets did not alter body weight or growth. HOSO-P and HOSO-F rats showed reduced total cholesterol (T-chol), non-high-density lipoprotein-cholesterol (non-HDL-chol) and triglycerides and increased HDL-chol levels, comparably to the OO rats. Total body fat (%) was similar among all rats; but HOSO-F showed the lowest intestinal, epididymal and perirenal fat. However, bone mineral content and density, and bone yield stress and modulus of elasticity were unchanged. Growing hypercholesterolemic rats fed HOSO with P or F improved serum lipids and fat distribution, but did not influence material bone quality.

Effect of chronic undernutrition on body mass and mechanical bone quality under normoxic and altitude hypoxic conditions.

Both undernutrition and hypoxia exert a negative influence on both growth pattern and bone mechanical properties in developing rats. The present study explored the effects of chronic food restriction on both variables in growing rats exposed to simulated high-altitude hypoxia. Male rats (n 80) aged 28 d were divided into normoxic (Nx) and hypoxic (Hx) groups. Hx rats were exposed to hypobaric air (380 mmHg) in decompression chambers. At T0, Nx and Hx rats were subdivided into four equal subgroups: normoxic control and hypoxic controls, and normoxic growth-restricted and hypoxic growth-restricted received 80 % of the amount of food consumed freely by their respective controls for a 4-week period. Half of these animals were studied at the end of this period (T4). The remaining rats in each group continued under the same environmental conditions, but food was offered ad libitum to explore the type of catch-up growth during 8 weeks. Structural bone properties (strength and stiffness) were evaluated in the right femur midshaft by the mechanical three-point bending test; geometric properties (length, cross-sectional area, cortical mass, bending cross-sectional moment of inertia) and intrinsic properties of the bone tissue (elastic modulus) were measured or derived from appropriate equations. Bone mineralisation was assessed by ash measurement of the left femur. These data indicate that the growth-retarded effects of diminished food intake, induced either by food restriction or hypoxia-related inhibition of appetite, generated the formation of corresponding smaller bones in which subnormal structural and geometric properties were observed. However, they seemed to be appropriate to the body mass of the animals and suggest, therefore, that the bones were not osteopenic. When food restriction was imposed in Hx rats, the combined effects of both variables were additive, inducing a further reduction of bone mass and bone load-carrying capacity. In all cases, the mechanical properties of the mineralised tissue were unaffected. This and the capacity of the treated bones to undergone complete catch-up growth with full restoration of the biomechanical properties suggest that undernutrition, under either Nx or Hx conditions, does not affect bone behaviour because it remains appropriate to its mechanical functions.

Monounsaturated fatty acids-rich diets in hypercholesterolemic-growing rats.

The effects of replacing dietary saturated fat by different monounsaturated fatty acid (ω-9MUFA) sources on serum lipids, body fat and bone in growing hypercholesterolemic rats were studied. Rats received one of the six different diets: AIN-93G (control, C); extra virgin olive oil (OO) + C; high-oleic sunflower oil (HOSO) + C or atherogenic diet (AT) for 8 weeks; the remaining two groups received AT for 3 weeks and then, the saturated fat was replaced by an oil mixture of soybean oil added with OO or HOSO for 5 weeks. Rats consuming MUFA-rich diets showed the highest body fat, hepatic index and epididymal, intestinal and perirenal fat, and triglycerides. T-chol and non-HDL-chol were increased in HOSO rats but decreased in OO rats. Bone mineral content and density were higher in both OO and HOSO groups than in AT rats. This study casts caution to the generalization of the benefits of MUFA for the treatment of hypercholesterolemia.

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

BACKGROUND: The 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. METHODS: Weanling 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 (7 mg/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. RESULTS: Food 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). CONCLUSIONS: This 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.

Atherogenic cholesterol-rich diet and periodontal disease.

OBJECTIVE: This study investigated the effect of an atherogenic cholesterol-rich diet (AT) on the alveolar bone loss in rats with ligature-induced experimental periodontitis (EP). METHODS: Female Wistar adult rats were assigned either a control (Co) or an AT diet fed for 9 weeks. The AT diet was high in saturated fat, cholesterol and energy. At week 2, animals were subjected to a unilateral ligature (L) around the left first molar (Co+L and AT+L). The contra lateral first right molar (not ligated) of both groups (Co and AT) were used as untreated controls. At week 9, blood was drawn, rats were euthanized, hemi-mandibles removed and stained digital photographs (buccal and lingual surfaces) and radiographs were obtained for quantification of alveolar bone loss (ABL). The ABL was determined by distance and area methods (mm(2)) and X-rays were used for periodontal bone support (PBS), (%). RESULTS: Rats in the AT group exhibited a 17% increase in energy intake, gained significant body weight and showed the highest serum total-cholesterol (T-C) and non-high density lipoprotein-cholesterol (HDL-C) levels (p<0.001). The amount of lost periodontal bone was the greatest in AT+L rats. AT feedings significantly increased the buccal area and distance of bone loss when compared with the unligated-teeth (p<0.001). The rats in the AT+L group also achieved the lowest percentage of PBS (p<0.001). The AT and Co+L rats showed similar PBS. This method more clearly elucidated the effect of the cholesterol-rich AT, with and without the influence of molar ligature, compared to the morphometric analysis. CONCLUSION: The alveolar bone loss of EP was magnified by ingestion of an atherogenic diet high in saturated fatty acids and cholesterol.

Prevalence of dyslipidemia and metabolic syndrome risk factor in overweight and obese children.

OBJECTIVE: To study the prevalence of dyslipidemia and metabolic syndrome risk factors in overweight/ obese children and adolescents. METHODOLOGY: The study included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who were overweight (n = 30) or obese (n = 109), based on BMI z score according to WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was considered when one or more serum lipids (mg/dL) were out of range: total cholesterol ≥ 200, high-density lipoprotein (HDL-C) ≤ 40, triglycerides (TG) > 110, low-density lipoprotein (LDL-C) > 130 or non-HDL-C > 145 and fasting blood glucose (FBG) > 110. Additional metabolic syndrome risk factors included: increased waist circumference (WC, ≥ 90th percentile) and high blood pressure (> 90th percentile). A history of low birth weight (< 2.5 kg) and a family history of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or type 2 diabetes mellitus (FHT2DM) were also assessed. RESULTS: The prevalence of dyslipidemia among overweight and obese children was 50.4% and its pattern was: hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non-HDL-C 15.8%, hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight (4.3%). Most children presented a variety of metabolic syndrome risk factors; only 25.8% did not have any such alterations identified. BMI z score showed a positive association with TG and negative with HDL-C. Overweight and obesity increased the odds ratios of metabolic syndrome risk factors, hypertriglyceridemia and low HDL-C. CONCLUSIONS: Overweight/obese children were prone to have dyslipidemia and metabolic syndrome. Excess body weight is an important harbinger of health that requires the assessment of multiple parameters to discern further health concerns that may be amenable to specific treatment.

[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol]. / Modificación del mecanismo operacional del mecanostato óseo en un modelo de estrés nutricional por efecto del propranolol.

INTRODUCTION: Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution. OBJECTIVE: To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress. MATERIAL AND METHODS: Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C 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 C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups. RESULTS: Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05). CONCLUSION: These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Dietas ricas en grasa y composición corporal a lo largo de dos generaciones. Estudio experimental / High-fat diets and body composition over two generations. An experimental study

Antecedentes y objetivo A pesar de los últimos avances acerca de los factores nutricionales que inducen modificaciones epigenéticas, la información en edades tempranas es escasa. El presente trabajo estudió en un modelo experimental a lo largo de dos generaciones las posibles modificaciones en la composición corporal, la posible expresión de cambios epigenéticos, y el resultado del consumo de dietas isocalóricas con niveles de grasa diferentes. Materiales y métodos Ratas Wistar hembras al destete se dividieron en dos grupos que recibieron una dieta con 7 y 15% de grasa (rica en grasa). A los 70 días se aparearon (M1) y sus crías (C1) constituyeron la primera generación; C1 a los 70 días fueron apareadas (M2) y sus crías (C2) constituyeron la segunda generación. Al destete, se evaluaron tanto las madres como las crías (M1, M2 y C1, C2), el peso (P) y composición corporales % de grasa (% Gra), por método químico y contenido mineral óseo de esqueleto total (CMO) por densitometría, expresado como %CMO. Resultados Al destete, en los grupos con dieta rica en grasa M2 y C2 (15% Gra) se observó un incremento significativo del P y % Gra (p<0,05), mientras que el aumento en el % Gra ya se observó en C1 y M1 (p<0,001). Por el contrario, el % CMO de M2 y C2 disminuyó significativamente (p<0,001).Conclusión este estudio pone de manifiesto la potencial necesidad de modificar ciertos hábitos alimentarios que eviten repetir patrones distorsionados de generación en generación (AU)

Introduction and objective Despite recent findings reported on the nutritional factors that induce epigenetic changes, little information is available at early ages. This study analyzed in an experimental model, over two generations, potential changes in body composition and potential expression of epigenetic changes as the result of the intake of isoenergetic diets with different fat levels. Materials and methods At weaning, Wistar female rats were divided into two groups that were fed either a control diet (fat=7% w/w) or a high-fat diet (15% w/w). Rats were mated at 70 days (M1) and their pups (P1) were the first generation; P1 rats were mated at 70 days (M2) and their pups (P2) represented the second generation. At weaning, mothers and pups (M1, M2 and P1, P2) were measured body weight (W) and composition (% body fat, %BF), and total skeleton bone mineral content (BMC), expressed as %BMC, using chemical and DXA methods respectively. Results At weaning, high-fat diet groups M2 and P2 showed significant increases in W and %BF (p<0.05); increased %BF values were already found in the M1 and P1 groups (p<0.001). By contrast, %BMC significantly decreased in M2 and P2 rats (p<0.001).Conclusion This study demonstrates the need to review certain eating habits to avoid perpetuation of unhealthy patterns generation after generation (AU)

[High-fat diets and body composition over two generations. An experimental study]. / Dietas ricas en grasa y composición corporal a lo largo de dos generaciones. Estudio experimental.

INTRODUCTION AND OBJECTIVE: Despite recent findings reported on the nutritional factors that induce epigenetic changes, little information is available at early ages. This study analyzed in an experimental model, over two generations, potential changes in body composition and potential expression of epigenetic changes as the result of the intake of isoenergetic diets with different fat levels. MATERIALS AND METHODS: At weaning, Wistar female rats were divided into two groups that were fed either a control diet (fat=7% w/w) or a high-fat diet (15% w/w). Rats were mated at 70 days (M(1)) and their pups (P(1)) were the first generation; P(1) rats were mated at 70 days (M(2)) and their pups (P(2)) represented the second generation. At weaning, mothers and pups (M(1), M(2) and P(1), P(2)) were measured body weight (W) and composition (% body fat, %BF), and total skeleton bone mineral content (BMC), expressed as %BMC, using chemical and DXA methods respectively. RESULTS: At weaning, high-fat diet groups M(2) and P(2) showed significant increases in W and %BF (p<0.05); increased %BF values were already found in the M(1) and P(1) groups (p<0.001). By contrast, %BMC significantly decreased in M(2) and P(2) rats (p<0.001). CONCLUSION: This study demonstrates the need to review certain eating habits to avoid perpetuation of unhealthy patterns generation after generation.

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 ß-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 ß-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.

Efecto de diferentes dosis de propranolol sobre la eficiencia estructural y mecánica esquelética en un modelo animal de retraso del crecimiento / Effect of different propranolol doses on skeletal structural and mechanic efficiency in an animal model of growth retardation

Objetivo Evaluar en un modelo de retraso del crecimiento (enanismo por desnutrición [ED]) el efecto de diferentes dosis de propranolol (P) sobre las variables antropo-morfométricas y biomecánicas del esqueleto apendicular. Materiales y métodos Ratas macho Wistar de 21 días se dividieron en grupos: control (C), C+P3,5 (CP3,5); C+P7 (CP7); C+P10,5 (CP10,5); C+P14 (CP14); ED, ED+P3,5 (EDP3,5); ED+P7 (EDP7); ED+P10,5 (EDP10,5) y ED+P14 (EDP14). Los animales controles con/sin P recibieron una dieta para roedores ad libitum; las ratas ED con/sin P recibieron por cada 100 g de peso corporal un 80% de la misma dieta durante 4 semanas (T4). Propranolol 3,5; 7; 10,5 y 14mg/kg/día fue inyectado intraperitonealmente 5 días/semana durante 4 semanas en CP3,5 y EDP3,5; CP7 y EDP7; CP10,5 y EDP10,5 y CP14 y EDP14, respectivamente. Resultados A T4, la restricción energética produjo efectos negativos sobre el crecimiento global, el fémur y su competencia mecánica. Propranolol mejoró la rigidez ósea en los animales ED con dosis de 7 y 10,5mg/kg/día, con un máximo de respuesta a 7mg/kg/día. Conclusiones El propranolol 7mg/kg/día sería la dosis más efectiva en la incorporación modelatoria de hueso con incremento de su eficiencia estructural y mecánica en el presente modelo animal de retraso del crecimiento. Dicho efecto podría ser el resultado del mantenimiento de la viabilidad del mecanosensor, de modificaciones de su sensibilidad, del punto de referencia biomecánico y/o de la respuesta de los efectores en las ratas ED(AU)

Objective To assess in a growth retardation (GR) model the impact of different propranolol (P) doses on anthropomorphometric and biomechanical variables of the appendicular skeleton. Materials and methods Twenty-one day-old male Wistar rats were divided into the following groups: control (C), C+P3.5 (CP3.5); C+P7 (CP7); C+P10.5 (CP10.5); C+P14 (CP14); ED, ED+P3.5 (EDP3.5); ED+P7 (EDP7); ED+P10.5 (EDP10.5), and ED+P14 (EDP14). Control animals with/without P were fed a rodent diet ad libitum. GR rats with/without P were given 80% of the same diet per 100g body weight for 4 weeks (T4). Propranolol 3.5, 7, 10.5, and 14mg/kg/day was intraperitoneally injected 5 days/week for 4 weeks to the CP3.5 and EDP3.5; CP7 and EDP7; CP10.5 and EDP10.5, and CP14 and EDP14 groups respectively. Results At T4, energy restriction had negative effects upon overall growth, femur, and its mechanical competence. Propranolol improved bone rigidity in GR animals at doses of 7 and 10.5mg/kg/day, with a maximum response at 7mg/kg/day. Conclusions Propranolol 7mg/kg/day would be the most effective dose for modeling incorporation of bone, as shown by the increased skeletal structural and mechanic efficiency in this animal model of growth retardation. Such effect may result from maintenance of mechanosensor viability, changes in its sensitivity, the biomechanical reference point and/or effector response in GR rats(AU)

[Effect of different propranolol doses on skeletal structural and mechanic efficiency in an animal model of growth retardation]. / Efecto de diferentes dosis de propranolol sobre la eficiencia estructural y mecánica esquelética en un modelo animal de retraso del crecimiento.

OBJECTIVE: To assess in a growth retardation (GR) model the impact of different propranolol (P) doses on anthropomorphometric and biomechanical variables of the appendicular skeleton. MATERIALS AND METHODS: Twenty-one day-old male Wistar rats were divided into the following groups: control (C), C+P3.5 (CP3.5); C+P7 (CP7); C+P10.5 (CP10.5); C+P14 (CP14); ED, ED+P3.5 (EDP3.5); ED+P7 (EDP7); ED+P10.5 (EDP10.5), and ED+P14 (EDP14). Control animals with/without P were fed a rodent diet ad libitum. GR rats with/without P were given 80% of the same diet per 100g body weight for 4 weeks (T4). Propranolol 3.5, 7, 10.5, and 14 mg/kg/day was intraperitoneally injected 5 days/week for 4 weeks to the CP3.5 and EDP3.5; CP7 and EDP7; CP10.5 and EDP10.5, and CP14 and EDP14 groups respectively. RESULTS: At T4, energy restriction had negative effects upon overall growth, femur, and its mechanical competence. Propranolol improved bone rigidity in GR animals at doses of 7 and 10.5mg/kg/day, with a maximum response at 7 mg/kg/day. CONCLUSIONS: Propranolol 7 mg/kg/day would be the most effective dose for modeling incorporation of bone, as shown by the increased skeletal structural and mechanic efficiency in this animal model of growth retardation. Such effect may result from maintenance of mechanosensor viability, changes in its sensitivity, the biomechanical reference point and/or effector response in GR rats.

[Neuronal LHRH system activity in an animal model of growth retardation]. / Actividad del sistema neuronal LHRH en un modelo animal de retraso del crecimiento.

OBJECTIVE: Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. MATERIAL AND METHODS: At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. RESULTS: At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. CONCLUSIONS: The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction.

Actividad del sistema neuronal LHRH en un modelo animal de retraso del crecimiento / Neuronal LHRH system activity in an animal model of growth retardation

Objetivo La restricción energética leve y crónica resulta en una enfermedad de origen nutricional, enanismo por desnutrición (ED), con retraso del crecimiento y del desarrollo puberal. Se evaluó el perfil de secreción hipotalámica de hormona liberadora de la hormona luteinizante, basal y por estimulación con glutamato en ratas ED a fin de dilucidar la disfunción gonadotrófica. Asimismo, se evaluó la capacidad reproductiva de dichos animales durante la realimentación. Materiales y métodos60 ratas de destete se dividieron en 2 grupos: Control (C) y experimental (ED). C fueron alimentadas a demanda libre con una dieta balanceada para roedores. ED recibió el 80% de la dieta consumida por C, durante 4 semanas (T4); A T4, ED fue alimentado a demanda libre por 8 semanas. Diez ratas de cada grupo fueron sacrificadas cada 4 semanas para los ensayos. Resultados A T4, peso y longitud corporal de ED frente a C disminuyeron significativamente (p<0,001). No se observaron cambios en la secreción basal, la frecuencia y la amplitud de pulsos de hormona liberadora de la hormona luteinizante de ED frente a C en ninguno de los tiempos estudiados. Por estimulación con glutamato, la secreción de hormona liberadora de la hormona luteinizante de ED frente a C fue significativamente mayor a T4 (p<0,05). Durante la realimentación, los ED alcanzaron el crecimiento compensador y la capacidad reproductiva. Conclusiones Los resultados sugieren una menor madurez del SNC en los animales ED después de la restricción en relación a su edad cronológica. El crecimiento somático adecuado y la capacidad reproductiva normal en las ratas ED realimentadas sugieren la reversibilidad de dichos procesos comprometidos por la restricción global, leve y crónica (AU)

Objective Mild and chronic energy restriction results in growth retardation with puberal delay, a nutritional disease known as nutritional dwarfing (ND). The aim of the present study was to assess the profile of hypothalamic luteinizing hormone-releasing hormone (LHRH) release, at baseline and under glutamate stimulation, in ND rats to elucidate gonadotrophic dysfunction. Reproductive ability during refeeding was also studied. Material and methods At weaning, 60 male rats were assigned to two groups of 30 animals each: a control and an experimental group. Control rats were fed ad libitum with a balanced rodent diet. The experimental group received 80% of the diet consumed by the control group for 4 weeks. After 4 weeks of food restriction, the ND group was fed freely for 8 weeks. Ten rats from each group were sacrificed every 4 weeks for assays. Results At week 4, body weight and length were significantly diminished in the experimental group vs. the control group (p<0.001). No changes were observed in LHRH baseline release, pulse frequency or amplitude in the experimental group compared with the control group at any time. However, under glutamate stimulation, LHRH release was significantly higher in ND rats than in control rats at week 4 (p<0.05). Refeeding the ND group allowed the rats to reach overall growth and reproductive ability. Conclusions The results of the present study suggest that the response to the facilitatory effect of glutamate on LHRH release in post-restricted ND rats is probably related to a lesser central nervous system maturation in relation to their chronological age. The adequate somatic growth and normal reproductive ability attained with refeeding suggest the reversibility of the two energetically costly processes compromised by global, mild and chronic food restriction (AU)

Improved bone status by the beta-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.