RESUMO
The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with CNI from January 2018 to June 2021. We collected patient demographics, anthropometric measures, and caloric and protein intake (enteral and parenteral) information during the first week of PICU admission. Goal adequacy for calories and protein was defined as [(intake/recommended) × 100] ≥ 60%. A total of 1112 patients were included in the nutrition assessment, 12% of whom were underweight (weight for age z score < -2). Of this group, 180 met the criteria for nutrition support evaluation. On the third day of admission, 50% of the patients < 2 years achieved caloric and protein goal adequacy, compared to 25% of patients > 2 years, with p-values of 0.0003 and 0.0004, respectively. Among the underweight patients, 60% achieved both caloric and protein goal adequacy by day 3 vs. 30% of non-underweight patients with p-values of 0.0006 and 0.002, respectively. The results show that achieving 60% of the recommended dietary intake by days 5 and 7 of admission was feasible in more than half of the patients in this cohort. Additionally, children who were evaluated by a clinical dietician during the first 48 h of PICU admission reached higher nutrition adequacy.
RESUMO
METHODS: An electronic, anonymous, multicenter survey housed by Monkey Survey was sent to physicians in LA and included questions about hospital and pediatric critical transport, resources available and level of car. Nineteen Latin-American countries were asked to complete the survey. RESULTS: A total of 212 surveys were analyzed, achieving a representativity of 19 LA countries, being most participants (59.4%, n = 126) from South America (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Paraguay, Peru, Uruguay and Venezuela). Most surveys were conducted by physicians of tertiary level centers (60.8%, n = 129), most of the institutions were classified by the participants as public health care centers (81.6%, n = 173). Most of the surveyed physicians (63.7%, n = 135) reported that there is a coordination center for critical care transport (CCT). In most cases, physicians report that a unified transport system for pediatric critical patients does not exist in their countries (67.45%, n = 143). Only 59 (30.7%) surveys reported the use of an exclusively pediatric critical care transport system. Most of these transport systems are described as a mixture of public and private efforts (51.56%, n = 99), but there is also a considerable involvement of government-funded critical transport systems (43.75%, n = 84). Specific training for personnel devoted to transportation of critically ill patients is reported in 55.6% (90), and the medical equipment necessary to carry out the transport is available in 67.7%. The majority (83.95%, n = 136) mentioned that access to advanced life support courses is possible. Training in triage and disaster is available in 44.1%. Physicians and registered nurse were identified as the transport providers in 41.5%, and only one third were made by pediatricians-pediatric nurse. The main reasons for transfers were respiratory illness, neonatal pathologies, trauma, infectious diseases, and neurological conditions. Overall, pediatric transport was reported as insufficient (70.19%, n = 148) by the surveyed physicians in LA and nonexisting by some of them (6.83%, n = 15). There were no regulations or laws in the majority of the surveyed countries (63.13%), and in the places where physicians reported regulatory laws, there were no dissemination (84.9%) by the local authorities. CONCLUSIONS: In LA, there is a great variability in personnel training, equipment for pediatric-neonatal transport, transport team composition, and characterization of critical care transport systems. Continued efforts to improve conditions in our countries by generating documents that standardize practices and generating scientific information on the epidemiology of pediatric transfers, especially of critically ill patients, may help reduce patient morbidity and mortality.
Assuntos
Cuidados Críticos , Grupos Raciais , Argentina , Criança , Humanos , América Latina , Inquéritos e QuestionáriosAssuntos
Insuficiência Respiratória , Desequilíbrio Hidroeletrolítico , Criança , Estado Terminal , Hidratação , Humanos , AutorrelatoRESUMO
Background: Orogastric tube feeding is indicated in neonates with an impaired ability to ingest food normally and can be administered with an intermittent bolus or continuous feeding schedule. Objectives: The objectives were to 1) compare the long-term effect of continuous with intermittent feeding on growth using the newborn pig as a model, 2) determine whether feeding frequency alters lean tissue and fat mass gain, and 3) identify the signaling mechanisms by which protein deposition is controlled in skeletal muscle in response to feeding frequency. Design: Neonatal pigs were fed the same amount of a balanced formula by orogastric tube either as an intermittent bolus meal every 4 h (INT) or as a continuous infusion (CON). Body composition was assessed at the start and end of the study by dual-energy X-ray absorptiometry, and hormone and substrate profiles, muscle mass, protein synthesis, and indexes of nutrient and insulin signaling were measured after 21 d. Results: Body weight, lean mass, spine length, and skeletal muscle mass were greater in the INT group than in the CON group. Skeletal muscle fractional protein synthesis rates were greater in the INT group after a meal than in the CON group and were associated with higher circulating branched-chain amino acid and insulin concentrations. Skeletal muscle protein kinase B (PKB) and ribosomal protein S6 kinase phosphorylation and eukaryotic initiation factor (eIF) 4E-eIF4G complex formation were higher, whereas eIF2α phosphorylation was lower in the INT group than in the CON group, indicating enhanced activation of insulin and amino acid signaling to translation initiation. Conclusions: These results suggest that when neonates are fed the same amounts of nutrients as intermittent meals rather than continuously there is greater lean growth. This response can be ascribed, in part, to the pulsatile pattern of amino acids, insulin, or both induced by INT, which enables the responsiveness of anabolic pathways to feeding to be sustained chronically in skeletal muscle.
Assuntos
Composição Corporal/fisiologia , Compartimentos de Líquidos Corporais/fisiologia , Comportamento Alimentar/fisiologia , Proteínas Musculares/metabolismo , Músculo Esquelético/fisiologia , Biossíntese de Proteínas , Aumento de Peso/fisiologia , Tecido Adiposo/metabolismo , Aminoácidos/sangue , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Compartimentos de Líquidos Corporais/metabolismo , Ingestão de Energia , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Feminino , Humanos , Recém-Nascido , Insulina/sangue , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais , Coluna Vertebral/crescimento & desenvolvimento , SuínosRESUMO
Sepsis disrupts skeletal muscle proteostasis and mitigates the anabolic response to leucine (Leu) in muscle of mature animals. We have shown that Leu stimulates muscle protein synthesis (PS) in healthy neonatal piglets. To determine if supplemental Leu can stimulate PS and reduce protein degradation (PD) signaling in neonatal muscle during endotoxemia, overnight-fasted neonatal pigs were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic-substrate clamps. Leu or saline was infused during the last hour. Markers of PS and PD were determined in skeletal muscle. Compared with controls, Leu increased PS in longissimus dorsi (LD), gastrocnemius, and soleus muscles. LPS decreased PS in these three muscles by 36%, 28%, and 38%, but Leu antagonized that reduction by increasing PS by 84%, 81%, and 83%, respectively, when supplemented to LPS. Leu increased eukaryotic translation initiation factor (eIF)3b-raptor interactions, eIF4E-binding protein-1, and S6 kinase 1 phosphorylation as well as eIF4E·eIF4G complex formation in LD, gastrocnemius, and soleus muscles of control and LPS-treated pigs. In LD muscle, LPS increased the light chain (LC)3-II-to-LC3 ratio and muscle-specific RING finger (MuRF-1) abundance but not atrogin-1 abundance or AMP-activated protein kinase-α phosphorylation. Leu supplementation to LPS-treated pigs reduced the LC3-II-to-LC3 ratio, MuRF-1 abundance, and AMP-activated protein kinase-α phosphorylation compared with LPS alone. In conclusion, parenteral Leu supplementation attenuates the LPS-induced reduction in PS by stimulating mammalian target of rapamycin complex 1-dependent translation and may reduce PD by attenuating autophagy-lysosome and MuRF-1 signaling in neonatal skeletal muscle.
Assuntos
Endotoxemia/metabolismo , Leucina/farmacologia , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Animais , Animais Recém-Nascidos , Autofagia/efeitos dos fármacos , Feminino , Lipopolissacarídeos/farmacologia , Masculino , Músculo Esquelético/efeitos dos fármacos , Miocárdio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sus scrofa , SuínosRESUMO
BACKGROUND: Acute infection promotes skeletal muscle wasting and insulin resistance, but the effect of insulin on energy and substrate sensing in skeletal muscle of chronically infected neonates has not been studied. METHODS: Eighteen 2-d-old pigs underwent cecal ligation and puncture (CLP) or sham surgery (CON) to induce a chronic infection for 5 d. On d 5, pancreatic-substrate clamps were performed to attain fasting or fed insulin levels but to maintain glucose and amino acids in the fasting range. Total fractional protein synthesis rates (Ks), translational control mechanisms, and energy sensing and degradation signal activation were measured in longissimus dorsi muscle. RESULTS: In fasting conditions, CLP reduced Ks and sirtuin 1 (SIRT1) and increased AMP-activated protein kinase α (AMPKα) activation and muscle RING-finger protein-1 (MuRF1). Insulin treatment increased Ks and mitochondrial protein synthesis, enhanced translation activation, and reduced SIRT1 in CON. In contrast, in CLP, insulin treatment increased Ks, protein kinase B (PKB) and Forkhead box O1 phosphorylation, antagonized AMPK activation, and decreased peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), MuRF1, and SIRT1. CONCLUSION: Energy and substrate sensing in skeletal muscle by the PKB-AMPK-SIRT1-PGC-1α axis is impacted by chronic infection in neonatal pigs and can be modulated by insulin.
Assuntos
Insulina/metabolismo , Músculo Esquelético/metabolismo , Peritonite/fisiopatologia , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Animais Recém-Nascidos , Glucose/metabolismo , Técnica Clamp de Glucose , Resistência à Insulina , Leucina/metabolismo , Peritonite/metabolismo , Fosforilação , Transdução de Sinais , Sirtuína 1/metabolismo , Sus scrofa , Suínos , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Sepsis induces loss of skeletal muscle mass by activating the ubiquitin proteasome (UPS) and autophagy systems. Although muscle protein synthesis in healthy neonatal piglets is responsive to amino acids (AA) stimulation, it is not known if AA can prevent the activation of muscle protein degradation induced by sepsis. We hypothesize that AA attenuate the sepsis-induced activation of UPS and autophagy in neonates. METHODS: Newborn pigs were infused for 8 h with liposaccharide (LPS) (0 and 10 µg·kg(-1)·h(-1)), while circulating glucose and insulin were maintained at fasting levels; circulating AA were clamped at fasting or fed levels. Markers of protein degradation and AA transporters in longissimus dorsi (LD) were examined. RESULTS: Fasting AA increased muscle microtubule-associated protein light 1 chain 3 II (LC3-II) abundance in LPS compared to control, while fed AA levels decreased LC3-II abundance in both LPS and controls. There was no effect of AA supplementation on activated protein kinase (AMP), forkhead box O1 and O4 phosphorylation, nor on sodium-coupled neutral AA transporter 2 and light chain AA transporter 1, muscle RING-finger protein-1 and muscle Atrophy F-Box/Atrogin-1 abundance. CONCLUSION: These findings suggest that supplementation of AA antagonize autophagy signal activation in skeletal muscle of neonates during endotoxemia.
Assuntos
Aminoácidos/sangue , Autofagia/efeitos dos fármacos , Endotoxemia/fisiopatologia , Insulina/sangue , Músculo Esquelético/patologia , Aminoácidos de Cadeia Ramificada/sangue , Animais , Animais Recém-Nascidos , Glicemia/análise , Nitrogênio da Ureia Sanguínea , Endotoxemia/sangue , Modelos Biológicos , Complexo de Endopeptidases do Proteassoma/metabolismo , Sepse/fisiopatologia , Sus scrofa , Suínos , TemperaturaRESUMO
Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11-12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 µmol·kg-1·h-1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were â¼25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were â¼30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2α, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v-ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates.
Assuntos
Leucina/farmacologia , Proteínas Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Alanina/farmacologia , Sistema A de Transporte de Aminoácidos/efeitos dos fármacos , Sistema A de Transporte de Aminoácidos/metabolismo , Animais , Animais Recém-Nascidos , Músculos do Dorso , Suplementos Nutricionais , Nutrição Enteral , Infusões Parenterais , Leucina/administração & dosagem , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Complexos Multiproteicos/efeitos dos fármacos , Complexos Multiproteicos/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas 90-kDa/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Proteínas Ribossômicas/efeitos dos fármacos , Proteínas Ribossômicas/genética , Sus scrofa , Suínos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Many low-birth-weight infants experience failure to thrive. The amino acid leucine stimulates protein synthesis in skeletal muscle of the neonate, but less is known about the effects of the leucine metabolite ß-hydroxy-ß-methylbutyrate (HMB). To determine the effects of HMB on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were infused with HMB at 0, 20, 100, or 400 µmol·kg body wt(-1)·h(-1) for 1 h (HMB 0, HMB 20, HMB 100, or HMB 400). Plasma HMB concentrations increased with infusion and were 10, 98, 316, and 1,400 nmol/ml in the HMB 0, HMB 20, HMB 100, and HMB 400 pigs. Protein synthesis rates in the longissimus dorsi (LD), gastrocnemius, soleus, and diaphragm muscles, lung, and spleen were greater in HMB 20 than in HMB 0, and in the LD were greater in HMB 100 than in HMB 0. HMB 400 had no effect on protein synthesis. Eukaryotic initiation factor (eIF)4E·eIF4G complex formation and ribosomal protein S6 kinase-1 and 4E-binding protein-1 phosphorylation increased in LD, gastrocnemius, and soleus muscles with HMB 20 and HMB 100 and in diaphragm with HMB 20. Phosphorylation of eIF2α and elongation factor 2 and expression of system A transporter (SNAT2), system L transporter (LAT1), muscle RING finger 1 protein (MuRF1), muscle atrophy F-box (atrogin-1), and microtubule-associated protein light chain 3 (LC3-II) were unchanged. Results suggest that supplemental HMB enhances protein synthesis in skeletal muscle of neonates by stimulating translation initiation.
Assuntos
Animais Recém-Nascidos/metabolismo , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Sus scrofa/metabolismo , Valeratos/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Leucina/metabolismo , Músculo Esquelético/química , Fatores de Iniciação de Peptídeos/análise , Fatores de Iniciação de Peptídeos/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Valeratos/sangueRESUMO
OBJECTIVE: To assess the effect of nutritional status and cardiovascular risk on hospital outcomes after congenital heart surgery in infants and children. DESIGN: Retrospective study. SETTING: Cardiac intensive care unit in a tertiary-care children's hospital. PATIENTS: One hundred twenty-one patients <24 months of age admitted to the cardiovascular intensive care unit (CVICU) for >48 hours following cardiac surgery. METHODS: Demographics, Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1), Paediatric Index of Mortality 2, and Pediatric Risk of Mortality III scores were obtained on admission. CVICU nutritional intake was calculated for 7 days. Energy and protein needs were estimated using recommended guidelines. Risk Adjustment for Congenital Heart Surgery-1 was categorized as (1-3) or (4-6). Malnutrition was categorized by Waterlow criteria and correlated with mortality risk, days of mechanical ventilation, and hospital and CVICU length of stay. RESULTS: Ninety-one patients who underwent cardiac surgery were categorized as RACHS-1 (1-3) and RACHS-1 scores of (4-6) (n = 30). Patients with RACHS-1 (4-6) had higher mortality risk by Pediatric Risk of Mortality III (4.9% vs. 2.6%, P < .01), longer CVICU (10.4 days vs. 4.8 days) and hospital stays (28 days vs.14 days), and more days of mechanical ventilation (4 days vs. 2 days) (all P < .005) than RACHS-1 (1-3). The prevalences of acute protein-energy malnutrition and chronic protein-energy malnutrition were 51.2% and 40.5%. The median hospital stay for mild, moderate, and severe chronic protein-energy malnutrition was 31, 10, and 22.5 days, respectively, vs. normal, 15 days (Kruskal-Wallis, P < .005). The average energy and protein requirements met on day 7 were 68 ± 27(SD)% and 68 ± 40%, respectively. CONCLUSION: Although nearly half of the patients were malnourished at surgery, only two-thirds of their recommended caloric and protein requirements were provided by week 1. To improve hospital outcomes, care should be taken to optimize the nutritional condition of infants and children prior to and following surgical correction of congenital heart disease to improve hospital outcomes.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Estado Nutricional , Apoio Nutricional , Desnutrição Proteico-Calórica/terapia , Doença Aguda , Fatores Etários , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Doença Crônica , Unidades de Cuidados Coronarianos , Ingestão de Energia , Metabolismo Energético , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/mortalidade , Hospitais Pediátricos , Humanos , Lactente , Tempo de Internação , Masculino , Avaliação Nutricional , Assistência Perioperatória , Prevalência , Desnutrição Proteico-Calórica/diagnóstico , Desnutrição Proteico-Calórica/mortalidade , Desnutrição Proteico-Calórica/fisiopatologia , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Centros de Atenção Terciária , Texas/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine infusion can be used to enhance protein synthesis during continuous feeding, neonatal piglets received the same amount of formula enterally by orogastric tube for 25.25 h continuously (CON) with or without LEU or intermittently by bolus every 4 h (BOL). For the CON+LEU group, leucine pulses were administered parenterally (800 µmol·kg(-1)·h(-1)) every 4 h. Insulin and glucose concentrations increased after the BOL meal and were unchanged in groups fed continuously. LEU infusion during CON feeding increased plasma leucine after the leucine pulse and decreased essential amino acids compared with CON feeding. Protein synthesis in longissimus dorsi (LD), gastrocnemius, and soleus muscles, but not liver or heart, were greater in CON+LEU and BOL than in the CON group. BOL feeding increased protein synthesis in the small intestine. Muscle S6K1 and 4E-BP1 phosphorylation and active eIF4E·eIF4G complex formation were higher in CON+LEU and BOL than in CON but AMPKα, eIF2α, and eEF2 phosphorylation were unchanged. LC3-II-to-total LC3 ratio was lower in CON+LEU and BOL than in CON, but there were no differences in atrogin-1 and MuRF-1 abundance and FoxO3 phosphorylation. In conclusion, administration of leucine pulses during continuous orogastric feeding in neonates increases muscle protein synthesis by stimulating translation initiation and may reduce protein degradation via the autophagy-lysosome, but not the ubiquitin-proteasome pathway.
Assuntos
Leucina/administração & dosagem , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Suínos/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Nutrição Enteral , Feminino , Glucagon/sangue , Insulina/sangue , Leucina/sangue , Leucina/metabolismo , Gravidez , Distribuição Aleatória , Suínos/sangueRESUMO
BACKGROUND: Continuous and intermittent bolus orogastric feedings are strategies used in infants unable to tolerate normal feeds. METHODS: To determine the effects of feeding modality on protein synthesis in different tissues, neonatal pigs received a balanced formula by orogastric tube as an intermittent bolus feed every 4 h or as a continuous infusion, or were fasted overnight. RESULTS: As compared with fasting, protein synthesis in gastrocnemius, masseter, and soleus muscles; left ventricle; liver; pancreas; jejunum; and kidney increased in bolus- and continuously fed pigs, but the greatest increase occurred after a bolus meal. Tuberous sclerosis complex (TSC2), the proline-rich AKT substrate of 40 kDa (PRAS40), eukaryotic initiation factor (eIF) 4E binding protein (4EBP1), and ribosomal protein S6 kinase 1 (S6K1) phosphorylation in all tissues, and the proportion of ribosomal protein S4 in liver polysomes were enhanced 90 min following the bolus meal but not immediately before the meal or during continuous feeding. Eukaryotic elongation factor 2 (eEF2) and eIF2α phosphorylation were unaffected by feeding. CONCLUSION: These results suggest that intermittent bolus feeding increases protein synthesis in muscles of different fiber types and visceral tissues to a greater extent than continuous feeding by stimulating translation initiation.
Assuntos
Métodos de Alimentação , Músculo Esquelético/fisiologia , Biossíntese de Proteínas/fisiologia , Vísceras/fisiologia , Análise de Variância , Animais , Animais Recém-Nascidos , Immunoblotting , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suínos , Fatores de TempoRESUMO
BACKGROUND: Critically ill children are at high risk of underfeeding and AKI, which may lead to further nutritional deficiencies. This study aimed to determine the adequacy of nutrition support during the first 5 days of intensive care unit (ICU) stay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A chart review of pediatric patients admitted to the pediatric ICU for >72 hours between August 2007 and March 2008 was conducted. Patients were classified as having no AKI versus AKI by modified pediatric RIFLE criteria. All nutrition was analyzed. Basal metabolic rate (BMR) was estimated by the Schofield equation and protein needs by American Society for Parenteral and Enteral Nutrition guidelines. RESULTS: Of the 167 patients, 102 were male and 65 were female (median age 1.4 years). Using the RIFLE criteria, 102 (61%) patients had no AKI, whereas 44 (26%) were classified as category R (risk), 12 (7%) as category I (injury), and 9 (5%) as category F (failure). The median 5-day energy intake was lower relative to estimated BMR. Overall protein provision (19%) was lower than energy provision (55%) compared with estimated needs (P<0.001). I/F patients were more likely to be fasted versus receiving enteral/parenteral nutrition (n=813 patient days) and to receive <90% of BMR (n=832 patient days) than No AKI/R patients. CONCLUSIONS: Underfeeding, common in critically ill children, was accentuated in AKI. Protein underfeeding was greater than energy underfeeding in the first 5 days of PICU stay. Efforts should be made to provide adequate nutrition in ICU patients with AKI.
Assuntos
Injúria Renal Aguda/dietoterapia , Transtornos da Nutrição Infantil/prevenção & controle , Fenômenos Fisiológicos da Nutrição Infantil , Estado Terminal/terapia , Desnutrição Proteico-Calórica/prevenção & controle , Criança , Transtornos da Nutrição Infantil/dietoterapia , Pré-Escolar , Proteínas Alimentares/administração & dosagem , Metabolismo Energético , Feminino , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Avaliação Nutricional , Desnutrição Proteico-Calórica/dietoterapia , Estudos RetrospectivosRESUMO
INTRODUCTION: Leucine (Leu) activates mammalian target of rapamycin (mTOR) to upregulate protein synthesis (PS). RESULTS: PS in skeletal muscles, heart, liver, pancreas, and jejunum, but not kidney, were greater in low protein supplemented with Leu (LP+L) than LP, but lower than high protein (HP). In longissimus dorsi muscle, protein kinase B phosphorylation was similar in LP and LP+L, but lower than HP. Although less than HP, p70 ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E binding protein 1 (4EBP1) association with regulatory associated protein of mammalian target of rapamycin was greater in LP+L than LP, resulting in higher S6K1 and 4EBP1 phosphorylation. Feeding LP+L vs. LP decreased 4EBP1·eIF4E and increased eIF4E·eIF4G formation, but not to HP. Similar results were obtained for S6K1 and 4EBP1 phosphorylation in gastrocnemius, masseter, heart, liver, pancreas, and jejunum, but not kidney. eIF2α and elongation factor 2 phosphorylation was unaffected by treatment. DICUSSION: Our results suggest that enteral Leu supplementation of a low protein diet enhances PS in most tissues through mTOR complex 1 pathways. METHODS: To examine enteral Leu effects on PS and signaling activation, 5-d-old piglets were fed for 24 h diets containing: (i) LP, (ii) LP+L, or (iii) HP.
Assuntos
Leucina/uso terapêutico , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Aminoácidos/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Suplementos Nutricionais , Nutrição Enteral/métodos , Fator de Iniciação 4E em Eucariotos/química , Fator de Iniciação Eucariótico 4G/química , Fatores de Iniciação em Eucariotos/química , Glicólise , Insulina/sangue , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Suínos , Fatores de Tempo , Distribuição TecidualRESUMO
Orogastric tube feeding is indicated for neonates with impaired ability to ingest and can be administered by intermittent bolus or continuous schedule. Our aim was to determine whether feeding modalities affect muscle protein deposition and to identify mechanisms involved. Neonatal pigs were overnight fasted (FAS) or fed the same amount of food continuously (CON) or intermittently (INT; 7 × 4 h meals) for 29 h. For 8 h, between hours 20 and 28, pigs were infused with [(2)H(5)]phenylalanine and [(2)H(2)]tyrosine, and amino acid (AA) net balances were measured across the hindquarters. Insulin, branched-chain AA, phenylalanine, and tyrosine arterial concentrations and whole body phenylalanine and tyrosine fluxes were greater for INT after the meal than for CON or FAS. The activation of signaling proteins leading to initiation of mRNA translation, including eukaryotic initiation factor (eIF)4E·eIF4G complex formation in muscle, was enhanced by INT compared with CON feeding or FAS. Signaling proteins of protein degradation were not affected by feeding modalities except for microtubule-associated protein light chain 3-II, which was highest in the FAS. Across the hindquarters, AA net removal increased for INT but not for CON or FAS, with protein deposition greater for INT. This was because protein synthesis increased following feeding for INT but remained unchanged for CON and FAS, whereas there was no change in protein degradation across any dietary treatment. These results suggest that muscle protein accretion in neonates is enhanced with intermittent bolus to a greater extent than continuous feeding, mainly by increased protein synthesis.
Assuntos
Ingestão de Alimentos/fisiologia , Metabolismo/fisiologia , Proteínas Musculares/metabolismo , Transdução de Sinais/fisiologia , Algoritmos , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Western Blotting , Dieta , Fator de Iniciação 4E em Eucariotos/metabolismo , Jejum/fisiologia , Feminino , Membro Posterior/anatomia & histologia , Hidroxilação , Insulina/sangue , Masculino , Proteínas Musculares/biossíntese , Fenilalanina/metabolismo , Suínos , Fatores de Tempo , Tirosina/metabolismoRESUMO
Accretion rates of muscle protein are elevated in normal neonates, but this anabolic drive decreases with maturation. As this change occurs, it is not known whether development also influences muscle protein catabolism induced by sepsis. We hypothesize that protein degradation in skeletal muscle induced by endotoxemia becomes more severe as the neonate develops. Fasted 7- and 26-day-old pigs were infused for 8 h with LPS (0 and 10 µg·kg(-1)·h(-1)), while plasma amino acids (AA), 3-methylhistidine (3-MH), and α-actin concentrations and muscle protein degradation signal activation were determined (n = 5-7/group/age). Plasma full-length α-actin was greater in 7- than 26-day-old pigs, suggesting a higher baseline protein turnover in neonatal pigs. LPS increased plasma total AA, 3-MH, and full-length and cleaved α-actin in 26- than in 7-day-old pigs. In muscle of both age groups, LPS increased AMPK and NF-κB phosphorylation, the abundances of activated caspase 3 and E-3 ligases MuRF1 and atrogin1, as well as the abundance of cleaved α-actin, suggesting activation of muscle proteolysis by endotoxin in muscle. LPS decreased Forkhead box 01 (Fox01) and Fox04 phosphorylation and increased procaspase 3 abundance in muscle of 26-day-old pigs despite the lack of effect of LPS on PKB phosphorylation. The results suggest that skeletal muscle in healthy neonatal pigs maintains high baseline degradation signal activation that cannot be enhanced by endotoxin, but as maturation advances, the effect of LPS on muscle protein catabolism manifests its severity.
Assuntos
Animais Recém-Nascidos/metabolismo , Endotoxemia/metabolismo , Infecções por Escherichia coli/metabolismo , Metabolismo/fisiologia , Músculo Esquelético/metabolismo , Índice de Gravidade de Doença , Suínos/crescimento & desenvolvimento , Quinases Proteína-Quinases Ativadas por AMP , Actinas/sangue , Aminoácidos/sangue , Animais , Animais Recém-Nascidos/microbiologia , Caspase 3/metabolismo , Modelos Animais de Doenças , Endotoxemia/fisiopatologia , Endotoxinas/farmacologia , Infecções por Escherichia coli/fisiopatologia , Insulina/sangue , Metabolismo/efeitos dos fármacos , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , NF-kappa B/metabolismo , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Suínos/metabolismoRESUMO
Orogastric tube feeding, using either continuous or intermittent bolus delivery, is common in infants for whom normal feeding is contraindicated. To compare the impact of different feeding strategies on muscle protein synthesis, after withholding food overnight, neonatal pigs received a complete formula orally as a bolus feed every 4 h or were continuously fed. Protein synthesis rate and translational mechanisms in skeletal muscle were examined after 0, 24, and 25.5 h. Plasma amino acid and insulin concentrations increased minimally and remained constant in continuously fed compared to feed-deprived pigs; however, the pulsatile meal feeding pattern was mimicked in bolus-fed pigs. Muscle protein synthesis was stimulated by feeding and the greatest response occurred after a bolus meal. Bolus but not continuous feeds increased polysome aggregation, the phosphorylation of protein kinase B, tuberous sclerosis complex 2, proline-rich Akt substrate of 40 kDa, eukaryotic initiation factor (eIF) 4E binding protein (4EBP1), and rp S6 kinase and enhanced dissociation of the 4EBP1 ·eIF4E complex and formation of the eIF4E ·eIF4G complex compared to feed deprivation (P < 0.05). Activation of insulin receptor substrate-1, regulatory associated protein of mammalian target of rapamycin, AMP-activated protein kinase, eukaryotic elongation factor 2, and eIF2α phosphorylation were unaffected by either feeding modality. These results suggest that in neonates, intermittent bolus feeding enhances muscle protein synthesis to a greater extent than continuous feeding by eliciting a pulsatile pattern of amino acid- and insulin-induced translation initiation.
Assuntos
Animais Recém-Nascidos/genética , Dieta , Proteínas Musculares/biossíntese , Músculo Esquelético/fisiologia , Proteínas Quinases Ativadas por AMP/metabolismo , Aminoácidos/sangue , Animais , Glicemia/análise , Nutrição Enteral/métodos , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/metabolismo , Feminino , Insulina/sangue , Proteínas Substratos do Receptor de Insulina/metabolismo , Fator 2 de Elongação de Peptídeos/metabolismo , Fosforilação , Gravidez , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas/genética , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais , Suínos , Serina-Treonina Quinases TOR/metabolismoRESUMO
Protein synthesis (PS) increases after a meal in neonates, but the time course of the changes in PS in different tissues after a meal is unknown. We aimed to evaluate the changes in tissue PS, mammalian target of rapamycin complex 1 (mTORC1) activation, and proportion of ribosomal protein (rp) mRNAs in polysomes over 4 h after a bolus meal in neonatal pigs (n = 6/group; 5- to 7-d-old). The results show a more sustained increase in PS in glycolytic compared with mixed fiber type muscles and no changes in oxidative muscles. PS increased in liver, jejunum, and pancreas but not in kidney and heart. Feeding did not affect AMP-activated protein kinase or RAS-related GTP binding B activation. Phosphorylation of tuberous sclerosis complex 2, proline-rich Akt substrate of 40 kD, mTOR, eukaryotic initiation factor 4E binding protein, and rp S6 kinase 1 increased in all tissues after feeding. The proportion of mRNAs encoding rp S4 and S8 in liver polysomes increased within 30 min postfeeding. These results suggest that feeding stimulates mTORC1 signaling in muscle and viscera, but mTORC1 activation alone is not sufficient to stimulate PS in all tissues.
Assuntos
Ingestão de Alimentos/fisiologia , Músculo Esquelético/fisiologia , Biossíntese de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Vísceras/fisiologia , Animais , Animais Recém-Nascidos , Ativação Enzimática , Músculo Esquelético/anatomia & histologia , Polirribossomos/metabolismo , Distribuição Aleatória , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Suínos , Serina-Treonina Quinases TOR/genética , Vísceras/anatomia & histologiaRESUMO
In muscle, sepsis reduces protein synthesis (MPS) by restraining translation in neonates and adults. Even though protein accretion decreases with development as neonatal MPS rapidly declines by maturation, the changes imposed by development on the sepsis-associated decrease in MPS have not been described. Pigs at 7 and 26 d of age were infused for 8 h with lipopolysaccharide (LPS, endotoxin, 0 and 10 µg · kg⻹ · h⻹). Fractional MPS rates and translation eukaryotic initiation factor (eIF) activation in muscle were examined (n = 5-7/group). The LPS-induced decrease in MPS was associated with reduced ribosomal and translational efficiency, whereas the age-induced decrease in MPS occurred by decreasing ribosome number. Abundances of mammalian target of rapamycin (mTOR) and S6 decreased, and that of the repressor eIF4E · 4E-binding protein 1 (4EBP1) association increased in 26-d-old pigs--compared with 7-d-old pigs. LPS decreased the abundance of the active eIF4E ·eIF4G association and the phosphorylation of eIF4G across ages, whereas the abundance of eIF4G declined and eIF2α phosphorylation increased with age. Therefore, when lacking anabolic stimulation, the decrease in MPS induced by LPS is associated with reduced ribosomal efficiency and decreased eIF4E ·eIF4G assembly, whereas that induced by development involves reduced ribosomal number, translation factor abundance, and increased eIF2α phosphorylation.
Assuntos
Desenvolvimento Muscular/fisiologia , Proteínas Musculares/biossíntese , Biossíntese de Proteínas , Ribossomos/metabolismo , Sepse/fisiopatologia , Animais , Animais Recém-Nascidos/metabolismo , Glicemia/metabolismo , Quinase do Fator 2 de Elongação/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Fator de Iniciação Eucariótico 4G/metabolismo , Feminino , Insulina/metabolismo , Lipopolissacarídeos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Gravidez , Distribuição Aleatória , Transdução de Sinais/fisiologia , SuínosRESUMO
Leucine is unique among the amino acids in its ability to promote protein synthesis by activating translation initiation via the mammalian target of rapamycin (mTOR) pathway. Previously, we showed that leucine infusion acutely stimulates protein synthesis in fast-twitch glycolytic muscle of neonatal pigs but this response cannot be maintained unless the leucine-induced fall in amino acids is prevented. To determine whether leucine can stimulate protein synthesis in muscles of different fiber types and in visceral tissues of the neonate in the long-term if baseline amino acid concentrations are maintained, overnight fasted neonatal pigs were infused for 24 h with saline, leucine (400 micromol kg(-1) h(-1)), or leucine with replacement amino acids to prevent the leucine-induced hypoaminoacidemia. Changes in the fractional rate of protein synthesis and activation of mTOR, as determined by eukaryotic initiation factor 4E binding protein (4E-BP1) and S6 kinase 1 (S6K1) phosphorylation, in the gastrocnemius and masseter muscles, heart, liver, jejunum, kidney, and pancreas were measured. Leucine increased mTOR activation in the gastrocnemius and masseter muscles, liver, and pancreas, in both the absence and presence of amino acid replacement. However, protein synthesis in these tissues was increased only when amino acids were infused to maintain baseline levels. There were no changes in mTOR signaling or protein synthesis in the other tissues we examined. Thus, long-term infusion of leucine stimulates mTOR signaling in skeletal muscle and some visceral tissues but the leucine-induced stimulation of protein synthesis in these tissues requires sustained amino acid availability.