RESUMEN
Acylcarnitine profiling by electrospray ionization tandem mass spectrometry (ESI-MS/MS) is a potent tool for the diagnosis and screening of fatty acid oxidation and organic acid disorders. Few studies have analyzed free carnitine and acylcarnitines in dried blood spots (DBS) of umbilical cord blood (CB) and the postnatal changes in the concentrations of these analytes. We have investigated these metabolites in healthy exclusively breastfed neonates and examined possible effects of birth weight and gestational age. DBS of CB were collected from 162 adequate for gestational age neonates. Paired DBS of heel-prick blood were collected 4-8 days after birth from 106 of these neonates, the majority exclusively breastfed. Methanol extracts of DBS with deuterium-labeled internal standards were derivatized before analysis by ESI-MS/MS. Most of the analytes were measured using a full-scan method. The levels of the major long-chain acylcarnitines, palmitoylcarnitine, stearoylcarnitine, and oleoylcarnitine, increased by 27, 12, and 109%, respectively, in the first week of life. Free carnitine and acetylcarnitine had a modest increase: 8 and 11%, respectively. Propionylcarnitine presented a different behavior, decreasing 9% during the period. The correlations between birth weight or gestational age and the concentrations of the analytes in DBS were weak (r £ 0.20) or nonsignificant. Adaptation to breast milk as the sole source of nutrients can explain the increase of these metabolites along the early neonatal period. Acylcarnitine profiling in CB should have a role in the early detection of metabolic disorders in high-risk neonates.
Asunto(s)
Femenino , Humanos , Recién Nacido , Masculino , Lactancia Materna , Carnitina/análogos & derivados , Sangre Fetal/química , Tamizaje Neonatal , Espectrometría de Masas en Tándem/métodos , Brasil , Carnitina/sangre , Pruebas con Sangre Seca/métodos , Ácidos Grasos/metabolismo , Estadísticas no Paramétricas , Espectrometría de Masa por Ionización de Electrospray/métodosRESUMEN
Acylcarnitine profiling by electrospray ionization tandem mass spectrometry (ESI-MS/MS) is a potent tool for the diagnosis and screening of fatty acid oxidation and organic acid disorders. Few studies have analyzed free carnitine and acylcarnitines in dried blood spots (DBS) of umbilical cord blood (CB) and the postnatal changes in the concentrations of these analytes. We have investigated these metabolites in healthy exclusively breastfed neonates and examined possible effects of birth weight and gestational age. DBS of CB were collected from 162 adequate for gestational age neonates. Paired DBS of heel-prick blood were collected 4-8 days after birth from 106 of these neonates, the majority exclusively breastfed. Methanol extracts of DBS with deuterium-labeled internal standards were derivatized before analysis by ESI-MS/MS. Most of the analytes were measured using a full-scan method. The levels of the major long-chain acylcarnitines, palmitoylcarnitine, stearoylcarnitine, and oleoylcarnitine, increased by 27, 12, and 109%, respectively, in the first week of life. Free carnitine and acetylcarnitine had a modest increase: 8 and 11%, respectively. Propionylcarnitine presented a different behavior, decreasing 9% during the period. The correlations between birth weight or gestational age and the concentrations of the analytes in DBS were weak (r ≤ 0.20) or nonsignificant. Adaptation to breast milk as the sole source of nutrients can explain the increase of these metabolites along the early neonatal period. Acylcarnitine profiling in CB should have a role in the early detection of metabolic disorders in high-risk neonates.
Asunto(s)
Lactancia Materna , Carnitina/análogos & derivados , Sangre Fetal/química , Tamizaje Neonatal , Espectrometría de Masas en Tándem/métodos , Brasil , Carnitina/sangre , Pruebas con Sangre Seca/métodos , Ácidos Grasos/metabolismo , Femenino , Humanos , Recién Nacido , Masculino , Espectrometría de Masa por Ionización de Electrospray/métodos , Estadísticas no ParamétricasRESUMEN
Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-α inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-α and IFN-γ in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 ± 11; male:female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 ± 11; male:female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-α and IFN-γ synthesis with the minimum dose used (50 µM). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 µM and the best inhibition of TNF-α production was achieved with 1 µM and for IFN-γ production it was 0.01 µM. The minimum dose of thalidomide used (1 µM) inhibited TNF-α production but thalidomide did not inhibit IFN-γ production even when the maximum dose (50 µM) was used. All drugs had an in vitro inhibitory effect on TNF-α production and, with the exception of thalidomide, all of them also decreased IFN-γ production.
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Antiinflamatorios/farmacología , Infecciones por HTLV-I/metabolismo , Inmunosupresores/farmacología , Interferón gamma/biosíntesis , Leucocitos Mononucleares/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Estudios de Casos y Controles , Colforsina/farmacología , Infecciones por HTLV-I/inmunología , Leucocitos Mononucleares/metabolismo , Pentoxifilina/farmacología , Rolipram/farmacología , Estadísticas no Paramétricas , Talidomida/farmacologíaRESUMEN
Human T lymphotropic virus type 1 (HTLV-1) is the causal agent of myelopathy/tropical spastic paraparesis (HAM/TSP), a disease mediated by the immune response. HTLV-1 induces a spontaneous proliferation and production of pro-inflammatory cytokines by T cells, and increasing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels are potentially involved in tissue damage in diseases related to HTLV-1. This exaggerated immune response is also due to an inability of the natural regulatory mechanisms to down-modulate the immune response in this group of patients. TNF-α inhibitors reduce inflammation and have been shown to improve chronic inflammatory diseases in clinical trials. The aim of this study was to evaluate the ability of pentoxifylline, forskolin, rolipram, and thalidomide to decrease in vitro production of TNF-α and IFN-γ in cells of HTLV-1-infected subjects. Participants of the study included 19 patients with HAM/TSP (mean age, 53 ± 11; male:female ratio, 1:1) and 18 HTLV-1 carriers (mean age, 47 ± 11; male:female ratio, 1:2.6). Cytokines were determined by ELISA in supernatants of mononuclear cell cultures. Pentoxifylline inhibited TNF-α and IFN-γ synthesis with the minimum dose used (50 µM). The results with forskolin were similar to those observed with pentoxifylline. The doses of rolipram used were 0.01-1 µM and the best inhibition of TNF-α production was achieved with 1 µM and for IFN-γ production it was 0.01 µM. The minimum dose of thalidomide used (1 µM) inhibited TNF-α production but thalidomide did not inhibit IFN-γ production even when the maximum dose (50 µM) was used. All drugs had an in vitro inhibitory effect on TNF-α production and, with the exception of thalidomide, all of them also decreased IFN-γ production.
Asunto(s)
Antiinflamatorios/farmacología , Infecciones por HTLV-I/metabolismo , Inmunosupresores/farmacología , Interferón gamma/biosíntesis , Leucocitos Mononucleares/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Estudios de Casos y Controles , Colforsina/farmacología , Femenino , Infecciones por HTLV-I/inmunología , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Pentoxifilina/farmacología , Rolipram/farmacología , Estadísticas no Paramétricas , Talidomida/farmacologíaRESUMEN
INTRODUCTION: The frequency and severity of salivary and lacrymal gland human T-cell lymphotropic virus type 1 (HTLV-1) infection were assessed in HTLV-1 plus patients, presenting with neurological deficit (tropical spastic paraparesis/HTLV-1 associated myelopathy [TSP/HAM]) or not. The mechanism of this deficit was investigated. MATERIAL AND METHODS: A case-control study was made from April 2002 to December 2005, in an area strongly endemic for HTLV-1. The patients were classified in three groups: group 1 with 16 patients presenting with TSP/HAM; group 2 with 67 HTLV-1 carriers and group 3 with 29 healthy volunteers. The dry syndrome was investigated by history taking and by oral and ophthalmological clinical examination. Immunological and biological screening for rhumatoid factors, antinuclear antibodies, and antibodies against soluble nuclear antigens (SSA, SSB). Peripheral blood was separated by density gradient and mononuclear cells were recovered to dose interferon-gamma and tumor necrosis factor-alpha. Patients in the three groups were assessed for salivary flow by stimulated weighing using Saxon's test. A Chi-2 test, a variance analysis (Anova), and the Spearman rank correlation test were used for the statistical analysis. RESULTS: The dry syndrome was mild and more common in group 1 patients (75%). In group 2, 22% of the patients presented with functional signs of buccal mucosa dryness comparable to those observed in group 1. No correlation was found between salivary flow and screened pro-inflammatory cytokines. DISCUSSION: Our results show that hyposialia is an important part of the disease induced by HTLV-1, even in virus carriers without neurological deficit. Its mechanism seems different than that of the Gougerot-Sjögren syndrome.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Enfermedades del Aparato Lagrimal/complicaciones , Enfermedades de las Glándulas Salivales/complicaciones , Adulto , Anciano , Anticuerpos Antinucleares/análisis , Autoantígenos/análisis , Brasil , Portador Sano , Estudios de Casos y Controles , Síndromes de Ojo Seco/complicaciones , Enfermedades Endémicas , Femenino , Humanos , Interferón gamma/análisis , Queratoconjuntivitis/complicaciones , Queratoconjuntivitis/fisiopatología , Enfermedades del Aparato Lagrimal/fisiopatología , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/complicaciones , Factor Reumatoide/análisis , Ribonucleoproteínas/análisis , Saliva/metabolismo , Enfermedades de las Glándulas Salivales/fisiopatología , Tasa de Secreción/fisiología , Factor de Necrosis Tumoral alfa/análisis , Xerostomía/complicaciones , Xerostomía/fisiopatología , Antígeno SS-BRESUMEN
Physical growth retardation is an early and prominent feature of zinc deficiency, but the effect of zinc supplementation in children is still not completely clear. This study investigated the impact of zinc supplementation on linear growth, growth velocity, IGF-I levels, and skeletal maturation of short children during and after mineral supplementation. The study was designed as a double-blind, randomized, controlled trial of zinc supplementation during a 6-month period, with a subsequent 6-month follow-up. Anthropometric data were collected at 0, 6, and 12 months. Measurements included plasma Zn, IGF-I, height, weight, triceps skinfold thickness, and body mass index. Eighteen healthy pre-pubertal short children (z-score -2.0) 7 to 10 years old with normal GH and IGF-I levels were randomized to two groups, one with zinc supplementation (5 mg/kg/d of ZnSO4) and the other with placebo. In the first 6 months, only height velocity increased significantly, 5.99+/-0.80 cm/yr vs 5.05+/-0.85 cm/yr (p=0.03). After 12 months, height velocity returned to the initial values, 3.92+/-0.59 cm/yr vs 4.19+/-1.08 cm/yr (p=0.29). This study indicates that zinc supplementation increased growth velocity, but these effects did not persist after supplementation was discontinued.
Asunto(s)
Estatura/efectos de los fármacos , Desarrollo Infantil/efectos de los fármacos , Zinc/uso terapéutico , Niño , Método Doble Ciego , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Zinc/efectos adversos , Zinc/sangreRESUMEN
The contemporary medical practice is enrolled in the rigid principles of a technological order. In order that the development and organization of the technological order would take place, and also material and objetively made concrete, it was essential that their products represented a materialization of a certain concept of human body and of health. This paper intends to be an introductory study of certain conditions of possibility for the construction of this technological order in the area of health. Although this thought includes, necessarily, a historical dimension, we do not intend here a factual reconstitution that considers dates and personalities. Its immediate goal will be to focus a moment of rupture, in which the introduction of the new concept of motion generated a new conception of human physiology. So, more important than one specific theory--of the blood circulation--or its effective results, is to understand the process of arising and/or changing of the concepts that allowed it to exist originally.