RESUMEN
Bioartificial lungs re-engineered from decellularized organ scaffolds are a promising alternative to lung transplantation. Critical features for improving scaffold repopulation depend on the mechanical properties of the cell microenvironment. However, the mechanics of the lung extracellular matrix (ECM) is poorly defined. The local mechanical properties of the ECM were measured in different regions of decellularized rat lung scaffolds with atomic force microscopy. Lungs excised from rats (n=11) were decellularized with sodium dodecyl sulfate (SDS) and cut into ~7µm thick slices. The complex elastic modulus (G(∗)) of lung ECM was measured over a frequency band ranging from 0.1 to 11.45Hz. Measurements were taken in alveolar wall segments, alveolar wall junctions and pleural regions. The storage modulus (G', real part of G(∗)) of alveolar ECM was ~6kPa, showing small changes between wall segments and junctions. Pleural regions were threefold stiffer than alveolar walls. G' of alveolar walls and pleura increased with frequency as a weak power law with exponent 0.05. The loss modulus (Gâ³, imaginary part of G(∗)) was 10-fold lower and showed a frequency dependence similar to that of G' at low frequencies (0.1-1Hz), but increased more markedly at higher frequencies. Local differences in mechanical properties and topology of the parenchymal site could be relevant mechanical cues for regulating the spatial distribution, differentiation and function of lung cells.
Asunto(s)
Microambiente Celular/fisiología , Matriz Extracelular/fisiología , Matriz Extracelular/ultraestructura , Pulmón/fisiología , Pulmón/ultraestructura , Microscopía de Fuerza Atómica/métodos , Andamios del Tejido , Animales , Bioprótesis , Sistema Libre de Células/fisiología , Módulo de Elasticidad/fisiología , Análisis de Falla de Equipo , Dureza , Ensayo de Materiales , Ratas , Ratas Sprague-DawleyRESUMEN
We describe the identification and initial characterization of a novel cell type that seems to be present in all tissues. To date we have isolated what we term "spore-like cells" based on the characteristics described below. They are extremely small, in the range of less than 5 microm, and appear to lie dormant and to be dispersed throughout the parenchyma of virtually every tissue in the body. Being dormant, they survive in extremely low oxygen environments, as evidenced by their viability in tissues (even in metabolically very active tissues such as the brain or spinal cord) for several days after sacrifice of an animal without delivery of oxygen or nutrients. The spore-like cells described in this report have an exceptional ability to survive in hostile conditions, known to be detrimental to mammalian cells, including extremes of temperature. Spore-like cells remain viable in unprepared tissue, frozen at -86 degrees C (using no special preservation techniques) and then thawed, or heated to 85 degrees C for more than 30 min. Preliminary characterization of these cells utilizing basic and special stains, as well as scanning and transmission electron microscopy reveal very small undifferentiated cells, which contain predominantly nucleus within a small amount of cytoplasm and a few mitochondria. Focal periodic acid-Schiff and mucicarmine stains suggest a coating of glycolipid and mucopolysaccharide. In vitro, these structures have the capacity to enlarge, develop, and differentiate into cell types expressing characteristics appropriate to the tissue environment from which they were initially isolated. We believe that these unique cells lie dormant until activated by injury or disease, and that they have the potential to regenerate tissues lost to disease or damage.
Asunto(s)
Células Madre/citología , Animales , Mamíferos , Microscopía Electrónica , Células Madre/ultraestructuraRESUMEN
We postulated that nitrous oxide transfer into the pleural cavity can occur by diffusion from the alveoli, independent of vascular transport. Under general anaesthesia, six sheep were studied in two phases, a control and an experimental phase. The sheep were anaesthetized, intubated, and received positive pressure mechanical ventilation. A catheter was placed in the right pleural cavity and 150 ml air injected. The animals were ventilated with 100% oxygen. The inspired gas was changed to a mixture of 50% nitrous oxide and 50% oxygen, and the rate of increase of nitrous oxide concentration in the pleural space was measured. The animals were then ventilated with 100% oxygen and then killed by exsanguination while ventilation was continued. The inspired mixture was changed to 50% nitrous oxide and 50% oxygen and the rate of increase in nitrous oxide concentration was measured in the pleural space again. During venitilation with nitrous oxide in the living animals, the concentration of nitrous oxide in the pleural cavity increased rapidly and decreased to zero during ventilation with 100% oxygen. During ventilation without circulation, the rate of increase in the concentration of nitrous oxide in the pleural cavity was the same as in the control phase. This suggests that nitrous oxide enters the pleural space by diffusion, rather than by vascular delivery. This mechanism may explain the rapid increase in the volume of pneumothorax if nitrous oxide is given in the inspired gas.
Asunto(s)
Anestésicos por Inhalación/farmacocinética , Óxido Nitroso/farmacocinética , Pleura/metabolismo , Animales , Difusión , Oxígeno/sangre , OvinosRESUMEN
For in vivo cell implantation techniques to be successful, the energy and metabolic substrate requirement of the cells being grown must be met. Certain cells with high-energy requirements (e.g., hepatocytes, pancreatic island cells) experience a high degree of cell death after implantation due to a limited supply of oxygen. We proposed that the pleural cavity might be an oxygen-rich environment and hence an excellent site for cell implantation. To test the hypothesis that the delivery of oxygen to the pleural cavity is directly proportional to the inspired oxygen concentration we measured the pO(2) of saline instilled in the pleural cavity as compared to that of the peritoneal cavity. We postulated that the physiologic basis for any difference was the result of direct diffusion of oxygen into the pleural space across the alveoli. The study was conducted on sheep (n = 6), after induction of general anesthesia, in two phases, control and experimental. Saline was instilled into the peritoneal and pleural cavities via catheters, after equilibration at given FiO(2), the pO(2) of the paline aspirated from the two cavities was compared. In the experimental group, animals were sacrificed (no circulation) and ventilated. The same sequence of steps as in the control phase were repeated. In the control group, the pO(2) of saline aspirated from the pleural cavity approached the arterial pO(2) at all FiO(2) levels. The pO(2) of the peritoneal saline aspirate fell over time. In the experimental phase (no circulation), the pO(2) of the pleural cavity saline rose to >400 mm Hg. We conclude that this is a result of direct diffusion and is a potential source of unlimited oxygen supply not dependent on vascular supply.
Asunto(s)
Trasplante de Células , Trasplante de Islotes Pancreáticos , Trasplante de Hígado , Oxígeno/metabolismo , Cavidad Peritoneal , Pleura , Animales , Consumo de Oxígeno , OvinosRESUMEN
BACKGROUND: Burn patients have impaired myocardial function and decreased beta-adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic absorption of topically administered epinephrine that is given to limit blood loss during burn excision could affect perioperative management. The authors evaluated the effect of topical epinephrine administration to patients during burn excision on the lymphocytic beta-adrenergic response. METHODS: Fifty-five patients (age, 2-18 yr) with 20-90% body surface area burns received a standardized anesthetic for a burn excision procedure. Lymphocyte samples were taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or thrombin (controls, n = 12). Plasma epinephrine levels were measured by high-performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was assessed by measuring production of cyclic adenosine monophosphate (cAMP) after stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta-adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta-adrenergic receptor density. RESULTS: Epinephrine levels were elevated at 1 h (P < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients. Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients receiving epinephrine than in control patients on stimulation with isoproterenol (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration, production of cAMP decreased when compared with baseline in both control patients and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05), PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor content was not changed. CONCLUSIONS: Topical epinephrine to limit blood loss during burn excision resulted in significant systemic absorption and increased plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic cascade was induced by the administration of epinephrine reflected by increased cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h after the use of epinephrine or thrombin, indicating that epinephrine administration was not a causative factor.
Asunto(s)
Pérdida de Sangre Quirúrgica/prevención & control , Quemaduras/metabolismo , Desensibilización Inmunológica , Epinefrina/uso terapéutico , Receptores Adrenérgicos beta/efectos de los fármacos , Receptores Adrenérgicos beta/metabolismo , Administración Tópica , Adolescente , Análisis de Varianza , Quemaduras/terapia , Niño , Preescolar , Cromatografía Líquida de Alta Presión , AMP Cíclico/biosíntesis , Epinefrina/efectos adversos , Epinefrina/sangre , Epinefrina/farmacocinética , Femenino , Citometría de Flujo , Humanos , Lactante , Subgrupos Linfocitarios/efectos de los fármacos , Linfocitos/metabolismo , Masculino , Absorción CutáneaRESUMEN
The objective of this study was to present data that showed high frequency percussive ventilation (HFPV) was superior to traditional mechanical ventilation for the treatment of children with inhalation injuries. Inhalation injuries continue to be the number one cause of death of patients with thermal injuries in the United States. Therapy for this condition has consisted of conservative pulmonary toilet and mechanical ventilation. Despite improvements in the management of burn injury, patients with inhalation injury develop pneumonia and pneumothorax, leading to adult respiratory distress syndrome. Unfortunately, inhalation injury that is complicated by pneumonia has been shown to increase mortality by 60% in these patients. Cioffi has shown that prophylactic use of HFPV in adult patients with inhalation injury has been a successful method of reducing the incidence of pneumonia and mortality. The effects of HFPV on the incidence of pneumonia, peak inspiratory pressures, and arterial partial pressure of oxygen/fraction of inspired concentration of oxygen (P/F) ratios were retrospectively studied in 13 children with inhalation injuries and compared with historic controls treated with conventional mechanical ventilation. All patients were treated with our standard inhalation injury protocol and extubated when they met standard extubation criteria. Patients ranged in age from 6 to 9 years, and most had burns covering greater than 50% of their total body surface areas. No deaths occurred in either group, but the patients who were treated with HFPV had no cases of pneumonia (P < .05), better P/F ratios (P < .05), lower peak inspiratory pressures, and less work of breathing (P < .05) as compared with our control group. On the basis of our clinical experience and data, the use of HFPV seems to be an effective treatment for the reduction of pulmonary morbidity in pediatric patients with inhalation injuries.
Asunto(s)
Ventilación de Alta Frecuencia , Lesión por Inhalación de Humo/terapia , Estudios de Casos y Controles , Niño , Ventilación de Alta Frecuencia/métodos , Humanos , Incidencia , Neumonía/epidemiología , Respiración Artificial , Fenómenos Fisiológicos Respiratorios , Lesión por Inhalación de Humo/mortalidadRESUMEN
The ideal oral wound care analgesic for children should be palatable, provide potent analgesia of rapid onset and short duration, and require minimal, yet appropriate, monitoring. With use of a double-blinded crossover design, we compared the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) (approximately 10 micrograms/kg) with the efficacy and safety of oral hydromorphone (60 micrograms/kg) in 14 pediatric inpatients (ages 4 to 17 years) undergoing daily burn wound care in a ward setting. Pulse oximetry, vital signs, side effects, patient pain scores, and observer scores for cooperation, anxiety, and sedation were recorded. Pulse oximetry, vital signs, cooperation, sedation, incidence of nausea or vomiting, and the amount of time it took to resume normal activities were similar in both treatment groups. OTFC resulted in improved pain scores before wound care and improved anxiolysis during wound care, but at other points it was similar in effect to hydromorphone. We conclude that OTFC is a safe and effective analgesic, that it may provide minor improvements in analgesia and anxiolysis compared with hydromorphone, and that it offers a palatable alternative route of opioid administration without intravenous access for wound care procedures in children.
Asunto(s)
Analgésicos Opioides/administración & dosificación , Quemaduras/complicaciones , Fentanilo/administración & dosificación , Hidromorfona/administración & dosificación , Dolor/tratamiento farmacológico , Administración Oral , Adolescente , Analgesia/métodos , Analgésicos Opioides/efectos adversos , Unidades de Quemados , Niño , Preescolar , Estudios Cruzados , Método Doble Ciego , Femenino , Fentanilo/efectos adversos , Estudios de Seguimiento , Humanos , Hidromorfona/efectos adversos , Pacientes Internos , Masculino , Dolor/etiología , Dimensión del Dolor , Resultado del Tratamiento , Heridas y Lesiones/terapiaRESUMEN
Testosterone administration (T) increases lean body mass and muscle protein synthesis. We investigated the effects of short-term T on leg muscle protein kinetics and transport of selected amino acids by use of a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis (FSR) and breakdown (FBR) rates of skeletal muscle protein were also directly calculated. Seven healthy men were studied before and 5 days after intramuscular injection of 200 mg of testosterone enanthate. Protein synthesis increased twofold after injection (P < 0.05), whereas protein breakdown was unchanged. FSR and FBR calculations were in accordance, because FSR increased twofold (P < 0.05) without a concomitant change in FBR. Net balance between synthesis and breakdown became more positive with both methodologies (P < 0.05) and was not different from zero. T injection increased arteriovenous essential and nonessential nitrogen balance across the leg (P < 0.05) in the fasted state, without increasing amino acid transport. Thus T administration leads to an increased net protein synthesis and reutilization of intracellular amino acids in skeletal muscle.
Asunto(s)
Aminoácidos/metabolismo , Músculo Esquelético/metabolismo , Biosíntesis de Proteínas , Testosterona/farmacología , Adulto , Alanina/metabolismo , Aminoácidos/sangre , Transporte Biológico/efectos de los fármacos , Isótopos de Carbono , Arteria Femoral , Humanos , Inyecciones Intramusculares , Cinética , Leucina/metabolismo , Lisina/metabolismo , Masculino , Modelos Biológicos , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/efectos de los fármacos , Isótopos de Nitrógeno , Fenilalanina/metabolismo , Flujo Sanguíneo Regional , Análisis de Regresión , Testosterona/administración & dosificación , Testosterona/fisiología , Factores de Tiempo , TritioRESUMEN
Extracorporeal membrane oxygenation (ECMO) as a treatment for pulmonary failure from postshock respiratory distress in burned children recently has been shown to salvage patients who were thought to have more than a 90% chance of dying. We describe five burned children in whom severe respiratory failure--not responsive to medical management and maximal ventilatory support--developed, and who underwent ECMO treatment. Three (60%) cases involved flame burns, with significant inhalation injury as diagnosed after a bronchoscopy; mean age was 3 years (2 to 4 years), with a mean total body surface area (TBSA) burn of 32% (15% to 53%), mean third-degree burns of 25% (5% to 53%). Two (40%) cases involved scald burns; mean age was 6 years (7 months to 11 years), with a mean TBSA burn of 56.5% (43% to 70%), mean third-degree burns of 40% (10.5% to 70%). Outcome was poor for those burned children who received ECMO therapy after prolonged ventilatory support for smoke inhalation injury. Children who experience perfusion/reperfusion shock injury to the lungs as a result of delayed resuscitation of scald burns may have an improved chance of survival with short courses of ECMO regardless of the burn size.
Asunto(s)
Quemaduras/complicaciones , Oxigenación por Membrana Extracorpórea , Insuficiencia Respiratoria/terapia , Niño , Preescolar , Femenino , Guías como Asunto , Humanos , Lactante , Masculino , Respiración Artificial , Resucitación , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Pediatric burn injuries present a major challenge to the health care team, but an orderly, systematic approach can simplify the initial stabilization and management. A clear understanding of the pathology of burn injuries is essential in providing quality burn care in the prehospital setting and at the referring hospital. After the patient has been rescued from the offending agent, assessment of the burn victim begins with the primary survey and life-threatening injuries initially addressed first. This is followed by a secondary survey to document and treat other injuries or problems. Intravenous access may be established in concert with the local/regional medical control and appropriate fluid resuscitation begun. Burn wounds should be covered with clean, dry sheets, and the patient kept warm with blankets to prevent hypothermia. The patient should be transported to the local hospital ED in the most appropriate mode available. At the local hospital, it should be determined if the burn patient needs burn center care, using the ABA Guidelines. In preparing for and organizing the transfer of the burn victim, consideration must be given to the continued monitoring and management of the patient during transport. In transferring burn patients the same priorities developed for the prehospital management are still operative. During the initial assessment and treatment and throughout the transport, an adequate airway, breathing, circulation, fluid resuscitation, urine output, and pain control must be assured. Ideally, transport of burn victims will occur through and organized, protocol driven plan that includes specialized transport mechanisms and personnel. Successful transport of burn victims, whether in the pre-hospital phase or during inter-hospital transfer, requires careful attention to treatment priorities, protocols, and attention to detail.
Asunto(s)
Quemaduras/terapia , Tratamiento de Urgencia , Quemaduras/complicaciones , Niño , Humanos , Transporte de PacientesRESUMEN
Pathophysiologic changes associated with inhalation injury make mechanical ventilation in children a challenge. Decreased lung compliance and increased airway resistance after inhalation injury may lead to elevated airway pressures and barotrauma. Previous studies have shown significant decreases in the incidence of pneumonia and death in adult patients with inhalation injury treated with high-frequency percussive ventilation (HFPV) as compared with conventional mechanical ventilation (CMV). No studies to date have compared lung compliance, airway resistance, or work of breathing in children being treated with HFPV versus CMV. The purpose of this study was to evaluate lung compliance, airway resistance, and work of breathing in pediatric patients with inhalation injury who required mechanical ventilation. Ten children with bronchoscopically identified inhalation injury requiring mechanical ventilation were studied. Five children received CMV and five children received HFPV. All patients were treated according to our standard inhalation injury protocol. Based on our data and patient population, children receiving ventilation with the HFPV have a significant decrease in the work of breathing as compared with CMV.
Asunto(s)
Respiración Artificial , Lesión por Inhalación de Humo/fisiopatología , Trabajo Respiratorio , Adulto , Resistencia de las Vías Respiratorias , Niño , Preescolar , Femenino , Ventilación de Alta Frecuencia , Humanos , Rendimiento Pulmonar , Masculino , Respiración Artificial/métodos , Lesión por Inhalación de Humo/terapiaRESUMEN
Opiates remain the most common form of analgesic therapy in the burn patient today. Because of increased opiate requirements, optimal relief of burn pain continues to be a problem for these patients. The purpose of this article is to summarize those alternative pain control methods that appear in the literature. For instance, in minor burns acetominophen continues to be a useful first line analgesic. Non-steroidal anti-inflammatory drugs (NSAID) and benzodiazepine are generally combined with opiates while entonox seems to be used commonly in the adolescent patients to relieve procedural pain. Antidepressants appear to enhance opiate-induced analgesia while anticonvulsants are useful in the treatment of sympathetically maintained pain following burns. Ketamine has been extensively used during burn dressing changes but its psychological side-effects have limited its use. Clonidine, however, has shown promise in reducing pain without causing pruritus or respiratory depression. Other forms such as transcutaneous electrical nerve stimulation (TENS), psychological techniques, topical and systemic local anaesthetics are also useful adjuncts.
Asunto(s)
Analgesia/métodos , Quemaduras/complicaciones , Manejo del Dolor , Analgésicos/administración & dosificación , Analgésicos/uso terapéutico , Animales , Quemaduras/terapia , Quimioterapia Adyuvante , Vías de Administración de Medicamentos , Humanos , Dolor/etiología , Resultado del TratamientoRESUMEN
The care of children with burns represents a therapeutic dilemma for many practitioners who periodically work with thermally injured patients. In this article, the authors emphasize the pathophysiology of thermal injury with special attention to the burned child. Within this framework, pain control, resuscitation, wound care, and the importance of a "burn care team" are discussed as important factors in the care of these children.
Asunto(s)
Quemaduras/fisiopatología , Quemaduras/terapia , Manejo del Dolor , Grupo de Atención al Paciente , Quemaduras/metabolismo , Niño , Preescolar , Humanos , Lactante , Dolor/etiología , Fenómenos Fisiológicos de la PielRESUMEN
This retrospective review evaluated the pain management of 395 acutely burned pediatric patients who were treated by a pain management protocol emphasizing acetaminophen as the initial medication to control background pain. Pain was assessed by using standardized instruments based on observations by patients, nurses, and parents. Morphine was added when scheduled acetaminophen (10-15 mg/kg/4 hr) did not control background pain. Fifty percent of the children received only acetaminophen to control background pain. Younger children and children with the smallest burns, regardless of age, were likely to be managed with acetaminophen alone. Most peak serum concentrations of acetaminophen were less than 10 micrograms/mL. When needed, children also received medication for painful procedures, anxiety, and posttraumatic stress symptoms. These additional medications were not more frequently given to children receiving only acetaminophen for background pain. These data suggest that acetaminophen is a safe, useful medication for the control of post-burn background pain in some children.
Asunto(s)
Acetaminofén/uso terapéutico , Analgésicos no Narcóticos/uso terapéutico , Quemaduras/complicaciones , Dolor/tratamiento farmacológico , Niño , Preescolar , Humanos , Dolor/etiología , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the effects of aging on mechanisms of body energy regulation and thereby determine the causes of unexplained weight loss in older persons, a factor predisposing to premature death and disability. DESIGN: Dietary intervention study. SETTING: Metabolic ward and outpatient. PARTICIPANTS: The subjects were 35 healthy younger and older men of normal body weight consuming a diet of typical composition and performing usual activities. MAIN OUTCOME MEASURES: Subjects were either overfed by a mean (+/- SD) of 4.09 (+/- 0.26) MJ/d (n = 17) or underfed by 3.17 (+/- 0.68) MJ/d (n = 18) for 21 days. Measurements were made of changes in body weight, body composition, and energy expenditure during overfeeding or underfeeding, and of subsequent voluntary nutrient intakes and changes in body weight. RESULTS: There was no significant effect of aging on changes in body composition, body weight, or energy expenditure with overfeeding or underfeeding. However, following overfeeding, younger men exhibited spontaneous hypophagia, whereas the older men did not (mean [+/- SD] changes in energy intake relative to control values were -2.11 [+/- 2.18] and 1.55 [+/- 2.11] MJ/d, respectively; P = .006). As a result, the younger men lost the excess body weight gained during overfeeding but the older men did not. Similarly, following underfeeding, the younger men exhibited hyperphagia while the older men did not (mean [+/- SD] changes in energy intake relative to control values were 1.88 [+/- 2.31] and -0.52 [+/- 1.54] MJ/d, respectively; P = .02), and as a result the older men failed to regain the weight lost during underfeeding. CONCLUSIONS: These results in 35 men suggest that aging may be associated with a significant impairment in the ability to control food intake following overeating or undereating. Since overeating and undereating occur routinely as part of the normal pattern of energy regulation, the findings reported herein may help to explain the vulnerability of older persons to unexplained weight gain and weight loss.
Asunto(s)
Envejecimiento/fisiología , Ingestión de Alimentos , Ingestión de Energía/fisiología , Metabolismo Energético , Pérdida de Peso , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Composición Corporal , Humanos , Hiperfagia , Masculino , Aumento de PesoRESUMEN
We investigated plasma methionine and cysteine kinetics in eight healthy adult men receiving for 6 d each of five L-amino acid diets supplying 13 mg methionine.kg-1.d-1 without cystine or 6.5 mg methionine.kg-1.d-1 plus 0, 5.2, 10.5, or 20.9 mg cystine.kg-1.d-1. On the morning of day 7, primed, constant intravenous infusions of L-[2H3-methyl, 1-13C]methionine and L-[3,3-2H]cysteine were given for 8 h (for the first 3 h subjects remained in a fasted state and for the next 5 h received small, equal meals at hourly intervals to achieve a fed state). Methionine and cysteine fluxes and rate of methionine oxidation were estimated from plasma methionine and cysteine labeling and 13C in expired air. Methionine oxidation declined (P < 0.05) with lowered methionine intake. Cysteine flux was similar across diets and dietary cystine did not affect tracer methionine oxidation. If there is a sparing effect of dietary cystine on the methionine requirement in adults, it probably takes place during the "first-pass" removal of these amino acids within the splanchnic region.
Asunto(s)
Cisteína/sangre , Cistina/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Metionina/sangre , Adulto , Isótopos de Carbono , Deuterio , Humanos , Infusiones Intravenosas , Cinética , Masculino , Metionina/administración & dosificación , Oxidación-ReducciónRESUMEN
The effects of removing proline from the diet on plasma leucine and proline kinetics were investigated. After a 1-wk control period, during which young adult men received a diet containing a complete L-amino acid mixture, seven subjects were given for 4 wk a diet devoid of proline (group 1); six received a diet devoid of proline, arginine, aspartate, glutamate, and serine (group 2); and seven continued with the complete diet (group 3). At the end of the control and 4-wk periods subjects were given a continuous, (3-h fast, 5-h fed) intravenous infusion of L-[1-13C]leucine and L-[5,5-2H]proline. Plasma proline was reduced significantly, especially during the fed state, in groups 1 and 2 after the 4-wk diet periods. Small but statistically significant (P < 0.05) reductions occurred in nonoxidative leucine disappearance and leucine appearance during the fasted state in group 2. Proline fluxes decreased by approximately 50% in fasted and fed states in groups 1 and 2. Mean de novo proline synthesis during the fasted state declined markedly (P < 0.05) after 4 wk in groups 1 and 2.
Asunto(s)
Aminoácidos/administración & dosificación , Proteínas en la Dieta/administración & dosificación , Leucina/farmacocinética , Prolina/farmacocinética , Adulto , Caproatos/sangre , Humanos , Infusiones Intravenosas , Cetoácidos/sangre , Leucina/administración & dosificación , Leucina/sangre , Masculino , Prolina/administración & dosificación , Prolina/sangre , Método Simple CiegoRESUMEN
In a previous paper (Am J Clin Nutr 1993;58:670-83) we described results for plasma amino acid changes, leucine kinetics, and body leucine and nitrogen balance in 20 young men receiving diets for 3 wk. The diets were based on the 1985 FAO/WHO/UNU amino acid requirement pattern (modified FAO diet; n = 7), the Massachusetts Institute of Technology (MIT) requirement pattern (MIT diet; n = 7), or the egg-protein pattern (Egg diet; n = 6). It was concluded, in comparison with the MIT and Egg diets, that the modified FAO diet was not capable of maintaining body amino acid homeostasis or balance. Here we report results from tracer studies with L-[O-2H5]phenylalanine and [2H2]tyrosine that were carried out within the same experiment. The modified FAO diet failed to maintain a mean body phenylalanine balance as determined from rates of phenylalanine hydroxylation (corrected for deuterium-isotopekinetic effects); balance was achieved with the MIT and Egg diets. These results further underscore the inadequacy of the internationally proposed amino acid requirement pattern for healthy adults. We recommend interim use of the MIT, tentative amino acid requirement values in all considerations of adult human amino acid requirements and nutrition.
Asunto(s)
Aminoácidos/administración & dosificación , Dieta , Fenilalanina/farmacocinética , Tirosina/farmacocinética , Adulto , Proteínas Dietéticas del Huevo/administración & dosificación , Proteínas Dietéticas del Huevo/metabolismo , Ayuno/metabolismo , Homeostasis , Humanos , Hidroxilación , Infusiones Intravenosas , Masculino , Necesidades Nutricionales , Fenilalanina/administración & dosificación , Fenilalanina/sangre , Tirosina/administración & dosificación , Tirosina/sangreRESUMEN
We studied the effects of amount and source of nonspecific nitrogen (NSN) on the oxidation of leucine and hydroxylation of phenylalanine. In phase 1, seven adult males received for 6 d diets providing indispensable amino acid intakes to meet the 1985 FAO/WHO/UNU (FAO) requirements or our proposed requirement values (MIT). During one diet period with each diet, the NSN of the basal diets (total nitrogen intake: 107 mg N.kg-1.d-1) was increased to a total of 160 mg N.kg-1.d-1. On the morning of day 7, an 8-h constant intravenous tracer-infusion protocol (3-h fast; 5-h fed state) was conducted with L-[1-13C]leucine, L-[ring-2H5]phenylalanine, and L-[3,3,2H2]-tyrosine as tracers. In phase 2, six subjects were given three diets for 6 d, supplying 107 mg N.kg-1.d-1; NSN was a mixture of dispensable amino acids in which glutamine accounted for 0%, 12.5%, and 100% of total NSN. Leucine oxidation and phenylalanine hydroxylation rates and whole-body leucine and phenylalanine balances were unaffected by addition of supplemental NSN to the diets in phase 1 or by amino acid source of NSN in phase 2. Leucine and phenylalanine balances were lower (P < 0.05) for FAO compared with MIT diets.
Asunto(s)
Leucina/farmacocinética , Nitrógeno/metabolismo , Fenilalanina/farmacocinética , Tirosina/farmacocinética , Adulto , Aminoácidos/sangre , Dióxido de Carbono/metabolismo , Dieta , Humanos , Leucina/metabolismo , Masculino , Modelos Biológicos , Nitrógeno/administración & dosificación , Fenilalanina/metabolismo , Respiración , Tirosina/metabolismoRESUMEN
Twenty young men received an L-amino acid diet, supplying 140 mg N.kg-1 x d-1 and patterned as in the Egg diet for 1 wk, and then for 3 wk either a pattern based on international recommendations (modified FAO diet; n = 7), our new amino acid requirement pattern (MIT diet; n = 7), or the egg pattern (Egg diet; n = 6). At the end of the initial week, at 1 and 3 wk with the three experimental diets, and after 3 d after return to the Egg diet, an 8-h continuous intravenous infusion with [1-13C]leucine (3 h fast, 5 h fed while subjects received hourly meals supplying the equivalent of one-twelfth the daily intake) was conducted. After 3 wk with the different diets, mean daily leucine balances were lower (P < 0.01) with the FAO diet (-160 mumol.kg-1 x d-1) than with the MIT diet (-15 mumol.kg-1 x d-1). Together with changes in plasma amino acid profiles [eg, methionine increased (P < 0.05) during feeding with the FAO and Egg diets but not with the MIT diet; increased proline concentrations during the fed state (P < 0.05) with the FAO diet but not with the MIT or Egg diets] we interpret these findings to indicate that the FAO diet is not capable of maintaining amino acid homeostasis, as is the case with the MIT and Egg diets.