The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Influence of Maternal Body Fat on Levels of Insulin, Insulin-Like Growth Factor-1, and Obestatin.

BACKGROUND: Insulin, insulin-like Growth Factor-1 (IGF-1), and obestatin in human milk originate from the circulation. There is also limited knowledge about the influence of body fat on the levels of these hormones in human milk. RESEARCH AIM: To determine (1) the influence of body fat on levels of insulin, IGF-1, and obestatin in human milk and serum/plasma during the postpartum period; (2) the changes in the levels of these hormones in human milk and serum/plasma postpartum; and (3) the presence of IGF-1 mRNA in human milk. METHODS: In this prospective, longitudinal, observational cohort study, levels of insulin, IGF-1, and obestatin were measured up to 30 days postpartum in milk and serum/plasma of 58 participants with adequate (≤ 32%) or excess (> 32%) total body fat determined by electrical bioimpedance. Student's t test and repeated-measures analysis of variance were used to evaluate the differences between groups. Pearson's test was used to analyze the associations. RESULTS: The milk from participants with excess body fat had higher insulin and IGF-1 levels and lower obestatin levels than that of participants with adequate body fat at 3-7, 14-15, and 30 days postpartum (adjusted p < .001). The levels of insulin, IGF-1, and obestatin were significantly higher in human milk than in serum/plasma (p < .05) and correlated with maternal body fat (p < .001). CONCLUSIONS: Maternal body fat was associated with elevated insulin and IGF-1 levels and decreased obestatin levels in human milk up to 30 days postpartum.

Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.

Necrotizing enterocolitis (NEC) is an inflammatory bowel disease and a leading cause of morbidity and mortality in preterm infants. In this study, a randomized double-blind parallel-group (1:1) trial was carried out in two neonatal intensive care units of two tertiary hospitals. Two hundred and twenty-five preterm newborns with an expected functional gastrointestinal tract were recruited and received an enteral dose of 75 mg of docosahexaenoic acid (DHA)/kg body weight or high-oleic sunflower oil daily for 14 days from the first enteral feed after birth. Confirmed NEC was evaluated with Bell's scale from stage ≥ IIa. Two hundred and fourteen randomized infants were analyzed in terms of the intent-to-treat (DHA-group: n = 105; control-group: n = 109); data for two hundred infants were analysed per protocol. Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100; p = 0.007), with RR = 0.93 (95% CI 0.881 to 0.981), risk difference = -7%, (95% CI -12.00 to -1.99), and number needed-to-treat = 15 (95% CI 8.3 to 50). Intent-to-treat analysis showed a lower level of treatment failure in the DHA-group compared with the control-group (6/105 (6%) vs. 16/109 (15%); p = 0.03, RR = 0.905, (95% CI 0.826 to 0.991)). The results after multivariate-regression analysis remained significant. Adverse events (apart from the incidence of NEC) were not different between groups. A daily dose of DHA for 14 days starting with the first enteral feed may prevent NEC in preterm infants.

Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial.

INTRODUCTION: Cognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs' families. Programmes to prevent or delay OAs' cognitive and physical decline are scarce. METHODS AND ANALYSIS: A double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline-one programme with and another without caregiver participation-and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants' demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima-media thickness; (6) OAs' health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable. ETHICS AND DISSEMINATION: The study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04068376).

Natural History of Serum Enzyme Levels in Duchenne Muscular Dystrophy and Implications for Clinical Practice.

OBJECTIVE: In Duchenne muscular dystrophy, creatine kinase and transaminases are released into the circulation, indicating muscle injury. Their usefulness in monitoring muscle injury or disease progression has not yet been fully evaluated. Thus, this study examined serum creatine kinase and transaminase concentrations at different ages in patients with Duchenne muscular dystrophy and evaluated their association with muscle injury. DESIGN: This is a prospective cohort study that included 110 patients with Duchenne muscular dystrophy categorized by age groups. Creatine kinase and transaminases were quantified in the serum; the Vignos scale evaluated the muscle function. RESULTS: Creatine kinase and transaminase levels were higher in ambulatory than that in nonambulatory patients, which significantly decreased as age increased. Serum creatine kinase and transaminase concentrations were elevated in all ages, and those aged 3-4 yrs had the highest concentrations. Age and Vignos Scale were significantly correlated with creatine kinase and transaminase concentrations. Age, creatine kinase, and transaminases explained the 42.5% of loss of muscle function. CONCLUSIONS: This study added the knowledge on the natural history of Duchenne muscular dystrophy at different ages and confirmed that creatine kinase and transaminases decrease with age and loss of muscle function, making them generally inappropriate for monitoring response to therapy, although they are useful for the clinical diagnosis.

Enteral Docosahexaenoic Acid and Retinopathy of Prematurity: A Randomized Clinical Trial.

BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the retina of low-birth-weight preterm infants that potentially leads to blindness. Docosahexaenoic acid (DHA), is protective in experimental models, but its administration as part of parenteral nutrition has shown inconsistent results. We test the effect of enteral DHA to prevent ROP and/or severity and to reduce hospital stay. METHODS: This was a double-blind parallel clinical trial. Preterm infants (n = 110; 55 per group) with birth weight <1500 g but ≥1000 g were recruited in a neonatal intensive care unit. Infants were randomized to receive 75 mg of DHA/kg/d (DHA group) or high oleic sunflower oil (control group) for 14 days by enteral feeding. The effect of DHA was evaluated on any stage of ROP, severe ROP (stage ≥3) incidence, and hospital stay. Groups were compared with relative risk (RR) and 95% confidence interval (CI), Fisher's exact test, Student's t-test, or Mann-Whitney U-test, as appropriate. Logistic regression was applied to adjust for confounders. RESULTS: There was no difference between the DHA and control groups in ROP risk (RR for DHA = 0.79; 95% CI, 0.49-1.27; P = 0.33). However, patients who received DHA showed lower risk for stage 3 ROP (RR for DHA = 0.66; 95% CI, 0.44-0.99; P = 0.03). After adjusting for confounders, this decreased risk remained significant (adjusted odds ratio = 0.10; 95% CI, 0.011-0.886; P = 0.04). Hospital stay was similar between groups. CONCLUSION: Enteral DHA may reduce the incidence of stage 3 ROP.

Evidence of muscle loss delay and improvement of hyperinsulinemia and insulin resistance in Duchenne muscular dystrophy supplemented with omega-3 fatty acids: A randomized study.

BACKGROUND & AIMS: Duchenne Muscular Dystrophy (DMD) is the most prevalent dystrophy of childhood and is characterized by generalized motor delays due to progressive muscular weakness, leading to loss of muscle mass. Additionally, patients with DMD develop obesity, hyperinsulinemia, and Insulin Resistance (IR). Omega-3 Long-Chain PolyUnsaturated Fatty Acids (Ω-3LCPUFA) increase fat mass, decrease lean mass, and decrease hyperinsulinemia and IR. The aim of this study was to analyze the impact of Ω-3LCPUFA consumption on lean mass, fat mass, hyperinsulinemia, and IR in children with DMD. METHODS: This placebo-controlled, double-blind, randomized study was carried out in 28 patients with DMD supplemented with 2.9 g/d of Ω-3LCPUFA (n = 14) or sunflower oil (placebo, n = 14) during 6 months. Serum glucose and insulin were measured at baseline and thereafter at months 3 and 6 of the intervention to estimate IR by HOmeostasis Model Assessment. Body composition was assessed by Dual Energy X-ray Absorptiometry. RESULTS: The percentage of change in EicosaPentaenoic Acid (EPA) and DocosaHexaenoic Acid (DHA) in erythrocytes was significantly (p < 0.05) higher in boys who consumed Ω-3LCPUFA than in the placebo group. Lean mass and fat mass (both in g/kg of Body Weight [BW]) had a trend toward being higher (p = 0.07 at month 3 and p = 0.085 at month 6) and lower (p = 0.05 at month 3 and p = 0.085 at month 6) respectively, in boys with DMD supplemented with Ω-3LCPUFA compared with the placebo group. The loss of lean mass was delayed in the Ω-3LCPUFA group; it started at month 6 but, in placebo, it started at month 3 of supplementation in comparison with the baseline of each group. Fasting insulin, percentage of boys with hyperinsulinemia, and IR were similar between the placebo and Ω-3LCPUFA groups during the 6 months of supplementation. The percentage of boys with IR was significantly (p = 0.045) lower at month 6 of supplementation in the Ω-3LCPUFA group than in the placebo group. CONCLUSION: This study suggests that Ω-3LCPUFA (2.9 g/day) intake during 6 months likely slows the progression of muscle loss, decreases the fat mass, and reduces IR in boys with DMD. The findings of this study provide scientific background for conducting a randomized trial focused of confirming the possible beneficial role of Ω-3LCPUFA on the previously mentioned alterations mentioned in boys with early muscle damage (without fibrosis) DMD. This research was registered at clinicaltrials.gov (NCT018264229).

Gene polymorphisms of angiotensin-converting enzyme and angiotensinogen and risk of idiopathic ischemic stroke.

OBJECTIVE: The renin-angiotensin system (RAS) is a hormonal signaling mechanism implicated in the atherosclerosis and regulation of blood pressure. Angiotensin-converting enzyme (ACE) a key enzyme in the RAS, plays important roles in vascular remodeling atherosclerosis, and ischemic stroke. The aim of this study was to examine the possible contribution of the I/D in the ACE gene, M235T and T174M in the angiotensinogen (AGT) gene polymorphisms with ischemic stroke in young Mexican population. MATERIALS AND METHODS: A total of 224 patients with diagnosis of idiopathic ischemic stroke ≤45 years of age, and 224 controls matched by age and gender, were recruited from 2006 and 2016. The I/D, M235T and T174M polymorphisms were determined in all participants by PCR-RFLP. RESULTS: There was a significant difference in the M235T genotype distribution (p = 0.01) and allele frequency between two groups (p = 0.01). Also, we found a significant difference in the T174M genotype distribution (p = 0.01) and the allele frequency between groups; (p = 0.02). In contrast, in I/D polymorphism, there was a similar genotype distribution; (p = 0.20) and allele distribution (p = 0.20). There were independent factors for ischemic stroke: M235T and T174M polymorphisms, smoking, hypertension, and familial history of atherothrombotic disease. The AGT levels were increased in the group of patients with stroke compared with the control group, but the AGT levels were not influenced by the allele or genotype in each polymorphism. CONCLUSIONS: The M235T and T174M polymorphisms represented an increased risk for stroke in young Mexican individuals. In contrast, the I/D was not associated with in the same group of patients. The AGT levels were higher in the acute phase of stroke, but it was not determined by the polymorphisms.

Body composition and body mass index in Duchenne muscular dystrophy: Role of dietary intake.

INTRODUCTION: In Duchenne muscular dystrophy (DMD) muscle is replaced by adipose tissue. The role of dietary intake (DI) in DMD has not been evaluated. In this study we examined body composition, body mass index (BMI), and adequacy of DI in patients with DMD and evaluated the influence of DI on body composition. METHODS: Patients (n = 101; age 3-18 years; BMI 11.8-29.5 kg/m2 ) completed a dietary recall to determine DI and then underwent dual-energy X-ray absorptiometry to determine body composition. RESULTS: Preschool-age and school-age boys with DMD had high total energy intake. Protein intake per kilogram exceeded recommendations. As age increased, the percentage of boys with abnormal BMI and fat mass increased, while lean mass decreased. Dietary intake did not predict body fat or lean mass. DISCUSSION: Age-dependent changes in BD in boys with DMD may be due to endogenous metabolic factors related to the underlying disease process and to disease-related mobility impairments. Muscle Nerve 59:295-302, 2019.

Optimal Cut-off Points of Fasting and Post-Glucose Stimulus Surrogates of Insulin Resistance as Predictors of Metabolic Syndrome in Adolescents According to Several Definitions

OBJECTIVE: The aim of this study was to determine optimal cut-off points for fasting and post-glucose stimulus surrogates of insulin resistance to predict metabolic syndrome in adolescents according to several definitions. METHODS: One hundred fifty-five adolescents living in Mexico City were enrolled during 2011 and 2012. Waist circumference and blood pressure were recorded. Subjects received an oral glucose load of 1.75 g per kg up to a maximum dose of 75 g. Blood samples were drawn at baseline and 120 minutes. Concentrations of plasma glucose, triglycerides, high-density lipoprotein cholesterol and insulin were determined. RESULTS: The frequency of metabolic syndrome showed a large variability when using a variety of published definitions; in contrast, the optimal cut-off points for fasting insulin, homeostatic model assessment of insulin resistance and two-hour oral glucose tolerance test insulin were very similar in almost all the definitions considered and had adequate diagnostic performance: area under the curve >0.869, sensitivity >0.835 and specificity >0.755. Insulin resistance surrogates had substantial agreements with Ford, Cook and Salas definitions (Kappa~0.62; agreement~82%); moderate agreement was observed for International Diabetes Federation, Cruz and Ferranti definitions (Kappa~0.41­0.59; agreement~77%). CONCLUSION: Insulin resistance surrogates may be a better approach for metabolic syndrome assessment in an adolescent population because of reduced variability and a higher predictive value.

IL-17-differentiated macrophages secrete pro-inflammatory cytokines in response to oxidized low-density lipoprotein.

BACKGROUND: Cytokines and macrophages play a central role in the development of atherosclerosis. Interleukin (IL)-17 is a pro-inflammatory cytokine with differential effects on innate immune cells. We investigated the effects of IL-17 on macrophage differentiation and foam cell formation and activation in response to oxidized low-density lipoprotein (oxLDL). METHODS: Human monocytes were treated with IL-17 to induce macrophage differentiation. As controls, human monocytes were differentiated into M1 macrophages (M1) or M2 macrophages (M2). Subsequently, we analyzed the expression levels of markers such as CD80, CD36 and Toll-like receptors (TLRs) as well as foam cell formation and cytokines in M1, M2 and macrophages differentiated with IL-17 with or without oxLDL. RESULTS: The expression of M1 or M2 markers or cytokines was not induced in macrophages differentiated with IL-17. Macrophages differentiated with IL-17 formed few foam cells, with an average proportion of 20%, and expressed 3 times as much TLR2 and 3.8 times as much TLR4 as M0 macrophages. Additionally, macrophages differentiated with IL-17 acquired inflammatory capacity in response to oxLDL through the expression of specific markers, such as CD80, which increased 18-times compared with macrophages differentiated with IL-17 alone, and secreted 1.3 times less tumor necrosis factor (TNF)-α than M1. Additionally, oxLDL increased the levels of CD80, CD86 and IL-6 by 5.7, 2.8 and 1.4 times in M1 compared with M1 in the absence of oxLDL. In M2, oxLDL induced increases in the secretion of IL-6 and TNF-α that were 1.9 times and 1.2 times smaller, respectively, than those observed in M1. CONCLUSION: Our study demonstrates that differentiation of macrophages with IL-17 does not induce the expression of markers or cytokines characteristic of M1 or M2 and these macrophages form few foam cells; however, the expression of TLR is increased. Moreover, these macrophages acquire the inflammatory capacity as evidenced by the expression of costimulatory molecules and secretion of pro-inflammatory cytokines in response to oxLDL. These findings suggest that the activation of macrophages differentiated with IL-17 by oxLDL contributes to the inflammatory process of atherosclerosis.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

BACKGROUND: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. METHODS: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. RESULTS: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 µg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (ß = -27 µg/kg, p = 0.028; R2 model = 0.90) for shorter duration (ß = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. CONCLUSIONS: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

BACKGROUND: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery. METHODS: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied. RESULTS: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1ß+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1ß+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups. CONCLUSIONS: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.

The 13C-Glucose Breath Test for Insulin Resistance Assessment in Adolescents: Comparison with Fasting and Post-Glucose Stimulus Surrogate Markers of Insulin Resistance.

OBJECTIVE: To evaluate the use of the 13C-glucose breath test (13C-GBT) for insulin resistance (IR) detection in adolescents through comparison with fasting and post-glucose stimulus surrogates. METHODS: One hundred thirty-three adolescents aged between 10 and 16 years received an oral glucose load of 1.75 g per kg of body weight dissolved in 150 mL of water followed by an oral dose of 1.5 mg/kg of U-13C-Glucose, without a specific maximum dose. Blood samples were drawn at baseline and 120 minutes, while breath samples were obtained at baseline and at 30, 60, 90, 120, 150, and 180 minutes. The 13C-GBT was compared to homeostasis model assessment (HOMA) IR (≥p95 adjusted by gender and age), fasting plasma insulin (≥p90 adjusted by gender and Tanner stage), results of 2-h oral glucose tolerance test (OGTT), insulin levels (≥65 µU/mL) in order to determine the optimal cut-off point for IR diagnosis. RESULTS: 13C-GBT data, expressed as adjusted cumulative percentage of oxidized dose (A% OD), correlated inversely with fasting and post-load IR surrogates. Sexual development alters A% OD results, therefore individuals were stratified into pubescent and post-pubescent. The optimal cut-off point for the 13C-GBT in pubescent individuals was 16.3% (sensitivity=82.8% & specificity=60.6%) and 13.0% in post-pubescents (sensitivity=87.5% & specificity=63.6%), when compared to fasting plasma insulin. Similar results were observed against HOMA and 2-h OGTT insulin. CONCLUSION: The 13C-GBT is a practical and non-invasive method to screen for IR in adolescents with reasonable sensitivity and specificity.

The effect of gestational age on expression of genes involved in uptake, trafficking and synthesis of fatty acids in the rat placenta.

Gestation triggers a tight coordination among maternal tissues to provide fatty acids (FA) to the fetus through placental transport; however, there is insufficient evidence regarding regulation of proteins involved in placental transport of FA according to gestational age. The aim of this study was to determine the role of gestational age on the expression of genes involved in FA uptake, trafficking and synthesis in the rat placenta to support fetal demands. Gene expression of encoding proteins for placental transport and synthesis of FA was measured in placenta. Also, FA composition was measured in placenta, fetuses and newborns. mRNA expression of lipoprotein lipase (lpl) and fatp-1 (for uptake) was 4.4- and 1.43-fold higher, respectively, during late gestation than at P14, but expression of p-fabp-pm decreased 0.37-fold at late pregnancy in comparison with P14. Only mRNA fabp-4 member for trafficking of FA was 2.95-fold higher at late gestation than at P14. mRNA of fasn and elovl-6 participating in saturated FA and enzymes for the polyunsaturated FA synthesis were downregulated during late gestation and their regulator srebf-1c increased at P16. This study suggests that gestational age has an effect on expression of some genes involved in uptake, trafficking and synthesis of FA in the rat placenta; mRNA expression of lpl and, fatp-1 for uptake and fabp-4 implicated in trafficking was expressed at high levels at late gestation. In addition, placenta expresses the mRNAs involved in FA synthesis; these genes were expressed at low levels at late gestation. Additionally, mRNAs of Srebf-1c transcriptional regulator of desaturases and elongases was highly expressed during late gestation. Finally, these changes in the rat placenta allowed the placenta to partially supply saturated and monounsaturated FA to the fetus.

Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy.

Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16-74.69) and 50 (OR = 8.73; 95% CI = 1.17-65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

Ácido docosahexaenoico y ácido araquidónico en neonatos: ¿el aporte que reciben es suficiente para cubrir sus necesidades? / Docosahexaenoic acid in neonates: do they receive enough to reach their needs?

Se describen las bases fisiológicas de la acción de los ácidos grasos poliinsaturados de las familias n-6 y n-3, así como de sus productos finales: el ácido araquidónico y el ácido docosahexaenoico, respectivamente, para identificar su importancia durante la etapa fetal en las funciones estructurales críticas al llegar a las 40 semanas de gestación. El déficit de los ácidos grasos poliinsaturados se relaciona con patologías en los niños pretérmino que no lograron la acreción adecuada, como la retinopatía del prematuro, la enterocolitis necrosante o la displasia broncopulmonar, entre otras. Se analizan los trabajos que evalúan el efecto del suplemento con diferentes concentraciones de ácidos grasos poliinsaturados sobre funciones neurológicas y visuales y crecimiento en los recién nacidos. Se abordan las necesidades de ácido docosahexaenoico y ácido araquidónico en esta etapa de la vida, y se comparan con el aporte que se puede lograr mediante la alimentación con leche humana y con las diferentes fórmulas para recién nacidos pretérmino, término y lactantes. Dado que el niño pretérmino nace con deficiencias tisulares pero con requerimientos aumentados de estos ácidos grasos, parece ser insuficiente el aporte con las fórmulas suplementadas comerciales actuales. La recomendación final es la alimentación de los niños con leche humana, ofreciendo a la madre sugerencias de consumo de fuentes con alto contenido de ácido docosahexaenoico, sobre todo si su hijo fue pretérmino.

In this article we discuss the physiological bases of polyunsaturated fatty acids (PUFAs) from n-6 and n-3 families and their end products: arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively, to identify their importance in the fetal stage such as critical structural functions at 40 weeks of gestation. PUFA deficit is related to pathologies in preterm infants who did not achieve adequate accretion such as retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and bronchopulmonary dysplasia (BPD), among others. In addition, studies evaluating the effect of supplementation with different concentrations of PUFAs on neurological and visual function and growth in neonates are analyzed. We also address the needs of DHA and AA at this stage of life and compare the enteral intake achieved by human milk feeding and the different formulas for preterm and term infants. DHA concentration in breast milk is highly variable and its contribution may be insufficient in neonates. Preterm infant formulas can meet international recommendations of DHA and AA issued by different organizations but, due to preterm birth, these infants have scarce tissue reserves but increased requirements for these fatty acids. Thus, enteral intake using current supplemental formula feeding appears to be insufficient. The final recommendation is to feed neonates with human milk by offering information to mothers regarding food sources with high DHA content, especially in the case of preterm babies.

Effectiveness of four manual breast pumps for mothers after preterm delivery in a developing country.

BACKGROUND: Hospital-grade electric pumps may be useful to initiate and sustain adequate milk production for mothers who are unable to breast-feed their babies hospitalized at special care nurseries (SCN), but their cost is generally not affordable for SCN and for most mothers in developing countries. Therefore, manual breast pumps (MBPs) can be an alternative, but the best option is unknown considering clinical parameters and mothers' preference from among currently available MBPs. OBJECTIVE: To compare the effectiveness of four MBPs in terms of milk volume, nutritional composition, and breast emptying in order to assist in making a choice for health care personnel and mothers in SCN settings. Duration of expression and maternal preference were also evaluated as secondary outcomes. METHODS: Mothers of preterm infants used 4 MBPs in a random order, 2 with a squeeze-handle mechanism (Isis and Harmony) and 2 with a cylindrical mechanism (Little Heart and Evenflo), both at the hospital and in home settings using each pump over one 24-hour period. RESULTS: Milk volume, nutritional composition, breast emptying, and duration of expression were not different among MBPs. Scale of maternal preference rated higher those with the squeeze-handle mechanism than the cylindrical mechanism (p < 0.05). CONCLUSIONS: There was no difference found in the effectiveness across the four pumps tested. The mothers' rating for comfort and ease of use showed a marked difference between pumps. These factors, plus cost, need to be considered when evaluating manual pumps for use in SCN settings in developing countries.

Oral administration of docosahexaenoic acid attenuates interleukin-1ß response and clinical course of septic neonates.

OBJECTIVE: To analyze cytokine responses and the clinical course of septic neonates orally supplemented with docosahexaenoic acid as well as to evaluate fatty acid incorporation into leukocytes. METHODS: A quasiexperimental study was conducted in neonates who developed sepsis following a surgical procedure. Selected neonates were randomly assigned to receive 100 mg docosahexaenoic acid (G-DHA) daily or olive oil (G-OO) as placebo for 14 d throughout a sepsis episode. At selection (baseline), blood samples were obtained to determine interleukin-1 (IL-1)ß, interleukin-6 (IL-6), and tumor necrosis factor-α as well as the leucocyte fatty acid profile. Measurements were repeated at 7 (D7) and 14 d (D14) of follow-up. Within- and between-group comparisons were conducted with parametric statistics after logarithmic transformation. Repeated measurement analyses with a general linear model procedure were used, adjusting according to human milk intake, use of anti-inflammatory drugs, and nutritional status. RESULTS: Sixty-three neonates were included: 29 in G-DHA group and 34 in G-OO group. Although decreases of cytokines during hospitalization were similar in both groups, there was a greater decrease of IL-1ß in the G-DHA group than in the G-OO group after adjusting by confounders (P = 0.028). Leukocyte docosahexaenoic acid increased from 4.96 ± 2.96 at baseline to 5.52 ± 3.05 and 5.92 ± 2.8 at D7 and D14, respectively, in the G-DHA group (P = 0.044). Illness severity was inversely associated with the proportion of docosahexaenoic acid in leukocytes throughout follow-up (P = 0.034). CONCLUSIONS: Oral supplementation with docosahexaenoic acid to neonates attenuates IL-1ß response and the clinical course of sepsis. This may be an additional strategy to further benefit ill neonates even if they are not candidates for parenteral nutrition.

Correlación entre el gasto y el aporte de energía en neonatos hospitalizados en una unidad de cuidados intensivos / Correlation between energy consumption and intake in infants hospitalized in an intensive care unit

Introducción. Una alimentación adecuada es esencial en el manejo del niño en estado crítico. Este estudio analiza la correlación entre el aporte total de energía (ATE) y el gasto energético total (GET) de pacientes hospitalizados en una Unidad de Cuidados Intensivos Neonatales (UCIN), considerando si nació pretérmino (PT), recibió alimentación parenteral (AP), o tratamiento quirúrgico (TQ). Métodos. Estudio transversal con 29 pacientes evaluados después de alcanzar estabilidad hemodinámica y ventilatoria. El GET se estimó mediante calorimetría indirecta, y el ATE sumando la energía administrada por vía enteral y parenteral. El análisis estadístico incluyó correlación de Spearman, U Mann-Whitney, prueba exacta de Fisher y regresión múltiple. Resultados. Catorce pacientes nacieron PT, y 21 recibieron TQ. Al momento del estudio, 14 recibían AP y 63% estaban desnutridos. El ATE fue mayor para los PT (P =0.022), los de AP (P =0.038) y los de TQ (P =0.046); el GET fue mayor en los PT (P =0.003). La correlación entre GET y ATE fue significativa sólo para alimentación enteral (r =0.518, P =0.046). El ATE fue inadecuado en 85.1% de los pacientes. Conclusiones. El ATE para niños atendidos en la UCIN parece ser inadecuado cuando se calcula por ecuaciones; se sugiere utilizar la determinación del gasto energético por calorimetría indirecta por lo menos en pacientes bajo el régimen de AP total.

Introduction. An adequate feeding is essential in the management of critically ill infants. This study analyzes the association between total energy intake (TEI) and total energy consumption (TEC) of patients hospitalized in a neonatal intensive care unit (NICU) taking into account whether were born preterm (PT), received parenteral nutrition (PN), or underwent surgical treatment (ST). Methods. A cross-sectional design including 29 patients hospitalized in a NICU after hemodynamic and ventilatory stability was conducted. TEC was determined by indirect calorimetry and TEI by the summation of the energy administered by enteral and parenteral pathways. The statistical analysis included, Spearman correlation, U Mann-Whitney test, exact Fisher test, and multiple regression. Results. Fourteen patients were born PT, 21 underwent ST; 14 were under PN regime at the moment of the study and 63% were undernourished. TEI was higher in PT (P =0.022), PN (P =0.038), and ST (P =0.046) patients; TEC was greater only in PT infants (P =0.003). TEC correlated with TEI only in patients receiving enteral nutrition (r=0.518, P =046). TEI was inadequate in 85.1% of the patients. Conclusion. The amount of energy administered to patients hospitalized in the NICU is inadequate when it is estimated by standardized equations. We suggest determining TEC by indirect calorimetry at least in patients under total PN.