RESUMEN
Human milk neutrophils and macrophages were examined by flow cytometry to determine whether they displayed phenotypic markers of activation. The markers were CD11b and L-selectin, which are increased or shed, respectively, from the surface of activated neutrophils. Phenotypic features of milk neutrophils and macrophages were similar to blood neutrophils stimulated with fMLP: plasma membrane expression of CD11b was increased and L-selectin was decreased. After blood neutrophils were incubated in acellular milk, their expression of CD11b increased and L-selectin decreased. The activation was not affected by trypsin but was significantly decreased by treating acellular milk with chloroform or ether. Sedimentation studies suggested that particulate fractions of milk were active. Further, the activation was partly blocked by treating target blood neutrophils with cytochalasin B. Thus, human milk neutrophils are activated, and the activation may be due partly to phagocytosis of membranous structures in milk.
Asunto(s)
Moléculas de Adhesión Celular/biosíntesis , Antígeno de Macrófago-1/biosíntesis , Leche Humana/inmunología , Neutrófilos/inmunología , Citometría de Flujo , Humanos , Inmunofenotipificación , Selectina L , Activación de Macrófagos/fisiología , Leche Humana/citología , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/efectos de los fármacosRESUMEN
The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project.
Asunto(s)
Hemorragia Cerebral/diagnóstico , Imagen por Resonancia Magnética/métodos , Trombosis de los Senos Intracraneales/diagnóstico , Hemorragia Cerebral/diagnóstico por imagen , Ventrículos Cerebrales/patología , Femenino , Hematoma Epidural Craneal/diagnóstico , Hematoma Epidural Craneal/diagnóstico por imagen , Hematoma Subdural/diagnóstico , Hematoma Subdural/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Estudios Prospectivos , Factores de Riesgo , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/diagnóstico por imagen , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
One hundred neonates determined prospectively to be at risk for neurologic handicap underwent magnetic resonance imaging with a high-field (1.5 T) imager. Thirty-three demonstrated a total of 37 lesions consistent with hypoxic-ischemic encephalopathy, including periventricular leukomalacia (n = 12), basal ganglia hemorrhage (n = 5), multicystic encephalomalacia (n = 5), and focal parenchymal hemorrhage (n = 15). Diagnoses by ultrasonography and computed tomography were compared with those by magnetic resonance imaging in 29 and 17 infants, respectively. Ultrasonography agreed more frequently with magnetic resonance imaging than did computed tomography. Ultrasonography detected 79% of lesions demonstrated by magnetic resonance imaging whereas computed tomography detected only 41%. Periventricular leukomalacia was seen most often in preterm infants, basal ganglia hemorrhage and multicystic encephalomalacia primarily occurred in term infants, and focal parenchymal hemorrhage occurred at all gestational ages. Basal ganglia hemorrhage and multicystic encephalomalacia were strongly associated with histories of perinatal asphyxia, seizures, and early abnormal neurological status. All infants with basal ganglia hemorrhage (5/5) and multicystic encephalomalacia (5/5) and the majority with periventricular leukomalacia (9/12) and focal parenchymal hemorrhages (9/15) had developmental abnormalities at discharge.
Asunto(s)
Isquemia Encefálica/diagnóstico , Hemorragia Cerebral/diagnóstico , Encefalomalacia/diagnóstico , Imagen por Resonancia Magnética/métodos , Isquemia Encefálica/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Encefalomalacia/diagnóstico por imagen , Femenino , Humanos , Recién Nacido , Leucomalacia Periventricular/diagnóstico , Leucomalacia Periventricular/diagnóstico por imagen , Masculino , Estudios Prospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
During the past decade, considerable evidence has accrued regarding the immunologic uniqueness of human milk and of the important role that the immune system in human milk plays in protecting not only the mature, healthy newborn, but also the premature infant who is more prone to infections and the damage caused by inflammatory processes. However, there is a great deal more to learn about the prophylactic and therapeutic uses of human milk in low birth weight infants, including (1) the status of many of the host defense factors in preterm milk, (2) how to preserve the protective agents in human milk during processing and storage, (3) the dose and duration of treatment with human preterm or mature milk that will be needed to protect against a particular disorder, (4) whether non-maternal milk is as efficacious as maternal milk for these infants, and (5) in view of the concern of potential graft versus host reactions, whether it is desirable or contraindicated to maintain the leukocytes in human milk used to feed premature infants. These questions are not easily answered, but will be worthy considerations by neonatologists, clinical immunologists, epidemiologists, and others who are concerned with providing optimal nutritional/immunologic support for the premature infant.
Asunto(s)
Recien Nacido Prematuro/inmunología , Leche Humana/inmunología , Antiinflamatorios , Humanos , Inmunidad , Inmunidad Innata , Recién NacidoRESUMEN
BACKGROUND: Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. METHODS: Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargyglycine (PPG). Livers were then isolated and perfused. RESULTS: Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. CONCLUSION: Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.
Asunto(s)
Glutatión/metabolismo , Hiperoxia/metabolismo , Hígado/metabolismo , Alquinos/farmacología , Aminoácidos Sulfúricos/análisis , Animales , Bilis/efectos de los fármacos , Bilis/metabolismo , Butionina Sulfoximina/farmacología , Inhibidores Enzimáticos/farmacología , Glicina/análogos & derivados , Glicina/farmacología , L-Lactato Deshidrogenasa/metabolismo , Hígado/efectos de los fármacos , Masculino , Técnicas de Cultivo de Órganos , Oxígeno/administración & dosificación , Perfusión , Ratas , Ratas Sprague-DawleyRESUMEN
The use of central venous lines in neonatal intensive care is widespread. We report a series of 11 infants in whom extravasation of fluid developed presumably as a result of the central line. There were six cases of pericardial effusion with a 67% mortality rate and five cases of pleural effusion with no mortality, for a total extravasation incidence of 1.1% for central lines placed during a 5-year period. The highest incidence of effusion occurred with polyethylene catheters, but all types of catheters resulted in effusion. This report emphasizes the serious morbidity and mortality of these complications of central venous lines.
Asunto(s)
Cateterismo Venoso Central/efectos adversos , Extravasación de Materiales Terapéuticos y Diagnósticos/complicaciones , Enfermedades del Prematuro/etiología , Derrame Pericárdico/etiología , Extravasación de Materiales Terapéuticos y Diagnósticos/diagnóstico , Extravasación de Materiales Terapéuticos y Diagnósticos/mortalidad , Agua Pulmonar Extravascular , Edad Gestacional , Humanos , Incidencia , Recién Nacido , Recien Nacido Prematuro , Derrame Pericárdico/mortalidad , Tasa de SupervivenciaRESUMEN
Binding characteristics of the alpha 1-adrenergic radioloigand [3H]prazosin, and the muscarinic cholinergic radioligand, [3H]quinuclidinyl benzilate, were determined both in intact cell preparations of rat alveolar type II pneumocytes (TIIPs) and in membrane preparations of rat lung tissue. Binding in adult and neonatal (< 24 h postnatal age) rats was also compared. Binding affinities for both receptor classes on TIIPs and whole lung membrane preparations alike did not vary significantly with age. In lung membrane preparations, the concentrations of both receptor classes were higher in neonates than adults. In TIIPs, the alpha 1-adrenergic receptor concentration was higher in neonates, but muscarinic receptor concentration was higher in adults. To begin investigation of the functional significance of these receptors, the effects of alpha 1-adrenergic and muscarinic agonists on intracellular calcium ion concentration ([Ca2+]i) were also measured. Both agonists induced consistent increases in [Ca2+]i, which were blocked by respective antagonists. These data indicate the presence of receptors on TIIPs for alpha 1-adrenergic and muscarinic agonists that may influence cellular function via modulation of [Ca2+]i.
Asunto(s)
Envejecimiento/fisiología , Pulmón/citología , Alveolos Pulmonares/citología , Surfactantes Pulmonares/metabolismo , Receptores Adrenérgicos alfa 1/fisiología , Receptores Muscarínicos/fisiología , Animales , Animales Recién Nacidos , Calcio/metabolismo , Canales de Calcio/fisiología , Masculino , Prazosina/farmacocinética , Quinuclidinil Bencilato/farmacocinética , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-DawleyRESUMEN
Although prenatal steroid therapy is known to enhance in utero maturation of the surfactant and antioxidant enzyme systems, little is known about the effects of steroids on the antioxidant system after birth. We measured activities of the antioxidant enzymes, catalase, superoxide dismutase, and glutathione peroxidase, in lung homogenates from both preterm and term rat pups after prenatal dexamethasone treatment. Enzyme activities were measured at birth and after exposure to > 98% oxygen. Dexamethasone treatment resulted in significantly higher survival of the preterm pups at 24 h (91.3% for dexamethasone versus 57% for saline). In preterm pups, the activities of catalase and superoxide dismutase at birth were higher after dexamethasone treatment (p < 0.05). However, after 24 h of hyperoxic exposure, there were no differences in activities of any of the antioxidant enzymes between the dexamethasone and control groups of prematurely born pups. In term pups, antioxidant enzyme activities did not differ significantly at birth; nor did they differ after 24 to 72 h of hyperoxic exposure in the dexamethasone and control treatment groups. Our results indicate that although prenatal dexamethasone treatment augments survival and catalase and superoxide dismutase activities at birth in preterm rat pups, dexamethasone does not result in altered early postnatal antioxidant enzyme activities after exposure to hyperoxia.
Asunto(s)
Antioxidantes/metabolismo , Dexametasona/farmacología , Feto/efectos de los fármacos , Oxígeno , Animales , Animales Recién Nacidos , Catalasa/metabolismo , Femenino , Madurez de los Órganos Fetales/efectos de los fármacos , Feto/metabolismo , Glutatión Peroxidasa/metabolismo , Pulmón/efectos de los fármacos , Pulmón/embriología , Pulmón/enzimología , Embarazo , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismoRESUMEN
Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate.
Asunto(s)
Antioxidantes/metabolismo , Oxígeno , Alveolos Pulmonares/metabolismo , Animales , Animales Recién Nacidos , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Alveolos Pulmonares/citología , Ratas , Ratas Endogámicas , Superóxido Dismutasa/metabolismoRESUMEN
The mechanisms of the increased tolerance to hyperoxia of neonatal animals of many species is incompletely understood. To investigate the etiology of this difference we compared neutrophil entry into the lungs of neonatal and adult rats after hyperoxic exposure. Adult rats were studied after exposure to > or = 98% O2 for 60 h and neonatal rats after 3 and 7 d. Neonatal survival was prolonged compared with that reported for adult rats (77% after 7 d of exposure). In adult rats, there were significant increases in pulmonary neutrophils after 60 h of O2 exposure. In neonatal rats, these changes were not evident after 72 h of exposure, but pulmonary neutrophils increased after 7 d of hyperoxia. Before mortality, pulmonary neutrophils were distributed differently in the age groups. After 7 d of O2 exposure in the neonates, total neutrophil counts in lung tissue (21.92 +/- 7.29 per cm2 grid) and lung myeloperoxidase (0.085 +/- 0.02 U/mg protein) remained significantly lower than in adults after 60 h of O2 exposure (41.44 +/- 9.08 per cm2 grid and 0.411 +/- 0.085 U/mg protein, respectively). However, in histologic specimens, O2-exposed neonates had higher percentages of neutrophils free in the alveolar air space than did adults, corresponding to a trend toward higher neutrophil counts in bronchoalveolar lavage fluid in the neonates. It appears that, in addition to delay in neutrophil influx into the lung, neonatal rats have lowered retention of neutrophils to the alveolar tissue.
Asunto(s)
Envejecimiento/patología , Movimiento Celular/fisiología , Hiperoxia/patología , Pulmón/citología , Neutrófilos/fisiología , Animales , Animales Recién Nacidos , Peso Corporal/fisiología , Líquido del Lavado Bronquioalveolar/citología , Recuento de Leucocitos , Pulmón/crecimiento & desarrollo , Masculino , Tamaño de los Órganos/fisiología , Peroxidasa/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The pathogenesis of pulmonary oxygen toxicity is postulated to be related in part to neutrophil-mediated injury. This study examined the effect of a monoclonal antibody directed against the CD11a,b,c/CD18 glycoprotein complex (beta 2 leukocyte integrins) on oxygen-induced lung injury. M8, a monoclonal antibody that binds to the beta chain of the guinea pig leukocyte integrins that facilitate neutrophil adherence to vascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were injected with a noninhibitory antibody to the CD18 complex or with saline. Survival in oxygen was similar for animals treated with M8 when compared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bronchoalveolar lavage fluid (BALF) was higher in the three groups of oxygen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other oxygen-exposed groups. M8 antibody treatment did not decrease hyperoxia-induced neutrophil accumulation into the lung as assessed by myeloperoxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil counts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hyperoxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmonary oxygen toxicity.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antígenos CD/fisiología , Pulmón/efectos de los fármacos , Neutrófilos/fisiología , Oxígeno/efectos adversos , Edema Pulmonar/etiología , Receptores de Adhesión de Leucocito/fisiología , Animales , Antígenos CD18 , Citometría de Flujo , Cobayas , Pulmón/patología , Masculino , Edema Pulmonar/patología , Edema Pulmonar/terapiaRESUMEN
Ectodermal dysplasia is a heterogeneous disorder that includes a constellation of congenital malformations occasionally associated with mild to moderate immune dysfunction. In this report, we describe a female infant with ectodermal dysplasia who was found to have thymic hypoplasia but no other phenotypic features of the DiGeorge anomalad. She experienced Candida parapsilosis sepsis at 1 week of age and a skin infection with Mycobacterium chelonii at 6 months. The numbers of blood B cells were normal and serum immunoglobulins normal to slightly reduced, but serum antibody responses of all immunoglobulin isotypes to protein immunogens were absent. Blood T cells were profoundly reduced and proliferative responses of T cells to mitogens were blunted. In contrast, there was an increased number of natural killer (NK) cells and increased NK activity in the blood. Over the first year of life, some of the immunodeficiencies resolved. Although the numbers of blood T cells (17% of total lymphocytes) remained low, proliferative responses to mitogens normalized and specific antibody responses improved. It seems likely that the thymic hypoplasia in this case was due to a paucity of ectodermal elements in the developing thymus, and that the immune defects were largely secondary to that event. In that respect, this human model of ectodermal dysplasia and thymic hypoplasia resembled the ectodermal/thymic defects found in the nude mouse.