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El trastorno del espectro autista (TEA) es una condición crónica del neurodesarrollo caracterizada por déficits persistentes en la comunicación e interacción social y un patrón de intereses restringidos y/o comportamientos repetitivos que pueden afectar el funcionamiento del individuo en la vida diaria familiar y comunitaria. El diagnóstico oportuno intenta mejorar la trayectoria, reducir el impacto funcional y disminuir los efectos de condiciones médicas asociadas. El diagnóstico tardío de TEA es considerado como aquel realizado luego de los 6 años de edad, en coincidencia con el fin de la escolaridad inicial. Si bien esta edad puede resultar arbitraria lo que se busca es una generalización de aquellos casos en los que probablemente hubo múltiples pérdidas de oportunidades diagnósticas y terapéuticas. Objetivo: Reflexionar sobre los determinantes del diagnóstico tardío del TEA con el fin de proponer posibles soluciones a esta problemática. Desarrollo: A partir de tres viñetas clínicas de pacientes que recibieron el diagnóstico en nuestro servicio, luego de los 6 años de edad, nos proponemos identificar y analizar aquellos factores (motivos sociodemográficos, problemas organizacionales, en la etapa de evaluación diagnóstica, respecto al género, cuidadores/ familiares y características clínicas) que determinan la demora diagnóstica. Conclusiones: El diagnóstico tardío del TEA es una problemática compleja y multifactorial, que implica desafíos significativos en el desarrollo de los NNyA con esta condición, sus familias y su entorno. Es importante considerar las causas que demoran el diagnóstico, desde el ámbito clínico, familiar y socio-ambiental para poder intervenir oportunamente (AU)
Autism spectrum disorder (ASD) is a chronic neurodevelopmental condition characterized by persistent deficits in communication and social interaction and a pattern of restricted interests and/or repetitive behaviors that can affect the individual's daily functioning both at home and in the community. Early diagnosis is important to improve the developmental trajectory, reduce functional impairment, and decrease the impact of comorbid medical conditions. Delayed diagnosis of ASD is defined as a diagnosis made after the age of 6 years, coinciding with the end of preschool. Although this age may be arbitrary, it serves to encompass cases in which there were probably multiple missed diagnostic and therapeutic opportunities. Objective: To explore the causes of late diagnosis of ASD in order to propose possible solutions to this problem. Development: Based on three clinical vignettes of patients who were diagnosed at our department after 6 years of age, we aimed to identify and analyze factors influencing diagnostic delays. These factors included sociodemographic causes, organizational challenges, issues during the diagnostic workup, considerations related to gender, caregivers/families, and clinical characteristics. Conclusions: Delayed diagnosis of ASD is a complex and multifactorial problem leading to significant challenges in the development of children and adolescents with this condition as well as their families and their environment. Identification of the causes of diagnostic delay is important from the clinical, family and socio-environmental point of view, in order to start timely interventions (AU)
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Humanos , Lactante , Preescolar , Niño , Adolescente , Trastorno Autístico/diagnóstico , Diagnóstico Tardío , Trastorno del Espectro Autista/diagnóstico , Cuidadores , Factores SociodemográficosRESUMEN
Introducción: Los trastornos del desarrollo (TD) constituyen un motivo de consulta muy frecuente en la práctica pediátrica. El Hospital Garrahan recibe por demanda espontánea al servicio de Mediano Riesgo (MR) consultas de cuidadores con preocupaciones sobre el desarrollo de los niños, niñas y adolescentes (NNyA). Allí son valorados por pediatras clínicos, quienes realizan la interconsulta al servicio de Clínicas Interdisciplinarias del Neurodesarrollo (CIND) según necesidad (representan el 10% del total de consultas en MR). El objetivo del trabajo es comparar las características de los pacientes de MR que fueron consultados al área de Maduración de CIND durante el bimestre marzo/abril de 2016, 2021 y 2022. Materiales y métodos: estudio retrospectivo, observacional y comparativo. Se revisaron las historias clínicas analizando las siguientes variables: edad, procedencia, contar con pediatra de cabecera, cobertura de salud, motivo de consulta y sospecha diagnóstica. Resultados: La cantidad de consultas aumentó por encima del 20%, con un descenso en la mediana de edad de alrededor de un año. Aproximadamente el 70% de los pacientes procedían del conurbano en los tres períodos. Observamos un descenso respecto al número de NNyA con seguimiento pediátrico y cobertura social. El lenguaje y la conducta fueron los motivos más frecuentes de consulta y la mayor sospecha diagnóstica fue el Trastorno del Espectro Autista (TEA). Conclusiones: Los datos observados pueden relacionarse con el impacto de la pandemia así como también con las condiciones socio-económicas de los últimos cinco años, con un mayor conocimiento acerca del desarrollo y un probable aumento de la prevalencia de los TD (AU)
Introduction: Developmental disorders (DD) are a frequent reason for consultation in pediatric practice. The Garrahan Hospital receives spontaneous consultations at the department of Intermediate Risk (IR) from caregivers with concerns about the development of children and adolescents. At the IR department, children and adolescents are evaluated by clinical pediatricians, who consult with specialists at the Interdisciplinary Neurodevelopmental Clinic (INDC) as needed (accounting for 10% of the total number of consultations at the IR department). The aim of this study was to compare the characteristics of IR patients who were consulted at the INDC during the bimonthly period March/April 2016, 2021, and 2022. Materials and methods: a retrospective, observational, and comparative study was conducted. Medical records were reviewed analyzing the following variables: age, provenance, having a primary care pediatrician, healthcare insurance, reason for consultation, and diagnostic suspicion. Results: The number of consultations increased by over 20%, with a decrease in median age of around one year. Approximately 70% of the patients came from Greater Buenos Aires in the three periods. A decrease in the number of children and adolescents with pediatric follow-up and a social health insurance was observed. Language and behavior disorders were the most frequent reasons for consultation and autism spectrum disorder (ASD) was most often suspected. Conclusions: The observed data may be related to the impact of the pandemic as well as socio-economic conditions over the last five years, together with increased knowledge about development and a probable increase in the prevalence of ASD (AU)
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Humanos , Preescolar , Trastornos de la Conducta Infantil , Atención Ambulatoria , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/epidemiología , Trastorno del Espectro Autista , Trastornos del Desarrollo del Lenguaje , Enfermedad Crónica , Prevalencia , Estudios RetrospectivosRESUMEN
Epithelial cells from oral mucosa (EOM) are responsible for important functions, like the primary protection of oral mucosa against external aggressions building a mechanical barrier against microorganisms, mechanical damage, toxic material, thermal regulation and secretion of different classes of inflammatory mediators. EOM could be an interesting tool for cellular and molecular biology research. Usually, EOM are collected by a painful and invasive process. In this study, we propose an alternative method to cultivate EOM collected by non-invasive scraping method of oral mucosa. Papanicolaou staining showed mainly two kinds of epithelial cell population after EOM scraping. As result of the five culture methods tested here, our results revealed that the EOM were successfully cultured on a murine feeder layer. In addition, EOM could be frozen and thawed, without morphology changes and loss of viability. Our findings suggest that EOM can be considered as a good cell source for many purposes, such as genetic studies, diagnosis and cell therapy.
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Fibroblasts are cells widely used in cell culture, both for transient primary cell culture or permanent as transformed cell lines. Lately, fibroblasts become cell sources for use in disease modeling after cell reprogramming because it is easily accessible in the body. Fibroblasts in patients will maintain all genetic background during reprogramming into induced pluripotent stem cells. In spite of their large use, fibroblasts are obtained after an invasive procedure, a superficial punch skin biopsy, collected under patient's local anesthesia. Taking into consideration the minimum patient's discomfort during and after the biopsy procedure, as well as the aesthetics aspect, it is essential to reflect on the best site of the body for the biopsy procedure combined with the success of getting robust fibroblast cultures in the lab. For this purpose, we compared the efficiency of four biopsy sites of the body (skin from eyelid, back of the ear, abdominal cesarean scar and groin). Cell proliferation assays and viability after cryopreservation were measured. Our results revealed that scar tissue provided fibroblasts with higher proliferative rates. Also, fibroblasts from scar tissues presented a higher viability after the thawing process.
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OBJECTIVE: The physiological changes in serum triglycerides and body temperature that are induced by splenectomy are poorly understood. Therefore, the aim of this study was to investigate parameters related to lipid and glucose metabolism, as well as thermoregulation, in splenectomized mice. DESIGN AND METHODS: Splenectomized and sham-operated WT mice (C57Bl/6) and ob/ob mice were randomly divided and treated with a standard or high fat diet, and several metabolic parameters and the body temperature were investigated. RESULTS: Splenectomy induced a significant increase in triglyceride levels regardless of the diet. It was found that the splenectomized WT mice showed greater serum leptin and insulin levels compared with the sham-operated mice. Additionally, the body temperatures of the splenectomized WT mice were greater than the body temperatures of the control animals regardless of diet; this result too was observed without any significant change in the temperature of the splenectomized ob/ob animals. CONCLUSION: The results suggest that splenectomy interferes with serum triglyceride metabolism and body temperature regardless of the fat content in the diet and that leptin is involved in the regulation of body temperature related to splenectomy.
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Regulación de la Temperatura Corporal , Leptina/metabolismo , Bazo/metabolismo , Tejido Adiposo/metabolismo , Animales , Peso Corporal , Dieta Alta en Grasa , Ingestión de Alimentos , Glucosa/metabolismo , Insulina/metabolismo , Ratones , Ratones Endogámicos C57BL , Esplenectomía , Triglicéridos/metabolismoRESUMEN
INTRODUCTION: The use of bioadhesive hydrogels for skin care presents important advantages such as long residence times on the application site and reduced product administration frequency. OBJECT: The aim of the present work was to develop bioadhesive hydrogels for skin application, using caffeine as a model active ingredient. METHODS: Eight hydrogels were formulated using binary combinations of a primary polymer (carbomer homopolymer type C (Carbopol(®) 980) or kappa carrageenan potassium salt (Gelcarin(®) GP-812 NF)) and a secondary polymer (carbomer copolymer type B (Pemulen(™) TR-1), xanthan gum or guar gum). Hydrogels were characterized by means of physico-chemical (dynamic rheological measurements, spreadability and adhesion measurements) and sensory methods (projective mapping in combination with a check-all-that-apply (CATA) question). Caffeine hydrogels were formulated using two of the most promising formulations regarding adhesion properties and sensory characteristics. In vitro active ingredient release studies were carried out. RESULTS: Hydrogel formulations showed a prevalently elastic rheological behaviour. Complex viscosity of carbomer homopolymer type C hydrogels was higher than that of the kappa carrageenan hydrogels. Besides, complex viscosity values were dependent on the secondary polymer present in the formulation. Significant differences among hydrogels were found in detachment force, work of adhesion and spreading diameter results. Association of projective mapping with CATA allowed to determine similarities and dissimilarities among samples. Cluster analysis associated the samples in two groups. Two hydrogels were selected to study the release of caffeine. Both hydrogels presented similar release profiles which were well described by the Higuchi model. Caffeine release was exclusively controlled by a diffusive process. CONCLUSION: Physico-chemical and sensory techniques enabled the identification of bioadhesive hydrogel formulations with positive characteristics for cosmetic applications. Formulations which combined carbomer homopolymer type C with xanthan gum or with carbomer copolymer type B were the most promising for bioadhesive skin products. Caffeine release profiles of selected formulations were not statistically different. Both hydrogels gradually released the active ingredient, reaching approximately 80% within the first 5 h, and their profiles were well described by the Higuchi model. In this context, it could be concluded that the selected hydrogels are suitable bioadhesive hydrogel formulations for cosmetic application on the skin.
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Cosméticos , Hidrogeles , Adhesivos TisularesRESUMEN
Human pluripotent stem cells bring promise in regenerative medicine due to their self-renewing ability and the potential to become any cell type in the body. Moreover, pluripotent stem cells can produce specialized cell types that are affected in certain diseases, generating a new way to study cellular and molecular mechanisms involved in the disease pathology under the controlled conditions of a scientific laboratory. Thus, induced pluripotent stem cells (iPSC) are already being used to gain insights into the biological mechanisms of several human disorders. Here we review the use of iPSC as a novel tool for disease modeling in the lab.
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Modelos Biológicos , Enfermedades del Sistema Nervioso/patología , Células Madre Pluripotentes/patología , Diferenciación Celular , Proliferación Celular , Células Madre Embrionarias/patología , Humanos , FenotipoRESUMEN
Angiotensin I-converting enzyme (ACE) is recognized as one of the main effector molecules involved in blood pressure regulation. In the last few years some polymorphisms of ACE such as the insertion/deletion (I/D) polymorphism have been described, but their physiologic relevance is poorly understood. In addition, few studies investigated if the specific activity of ACE domain is related to the I/D polymorphism and if it can affect other systems. The aim of this study was to establish a biochemical and functional characterization of the I/D polymorphism and correlate this with the corresponding ACE activity. For this purpose, 119 male brazilian army recruits were genotyped and their ACE plasma activities evaluated from the C- and N-terminal catalytic domains using fluorescence resonance energy transfer (FRET) peptides, specific for the C-domain (Abz-LFK(Dnp)OH), N-domain (Abz-SDK(Dnp)P-OH) and both C- and N-domains (Abz-FRK(Dnp)P-OH). Plasma kallikrein activity was measured using Z-Phe-Arg-AMC as substrate and inhibited by selective plasma kallikrein inhibitor (PKSI). Some physiological parameters previously described related to the I/D polymorphism such as handgrip strength, blood pressure, heart rate and BMI were also evaluated. The genotype distribution was II n=27, ID n=64 and DD n=28. Total plasma ACE activity of both domains in II individuals was significantly lower in comparison to ID and DD. This pattern was also observed for C- and N-domain activities. Difference between ID and DD subjects was observed only with the N-domain specific substrate. Blood pressure, heart rate, handgrip strength and BMI were similar among the genotypes. This polymorphism also affected the plasma kallikrein activity and DD group presents high activity level. Thus, our data demonstrate that the I/D ACE polymorphism affects differently both ACE domains without effects on handgrip strength. Moreover, this polymorphism influences the kallikrein-kinin system of normotensive individuals.
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Mutación INDEL/genética , Peptidil-Dipeptidasa A/metabolismo , Calicreína Plasmática/metabolismo , Polimorfismo Genético/genética , Análisis de Varianza , Presión Sanguínea/genética , Transferencia Resonante de Energía de Fluorescencia , Genotipo , Fuerza de la Mano/fisiología , Frecuencia Cardíaca/genética , Humanos , Masculino , Peptidil-Dipeptidasa A/genética , Calicreína Plasmática/genética , Adulto JovenRESUMEN
Bcr-Abl is one of the most potent antiapoptotic molecules and is the tyrosine-kinase implicated in Philadelphia (Ph) chromosome-positive leukemia. It is still obscure how Bcr-Abl provides the leukemic cell a strong resistance to chemotherapeutic drugs. A rational drug development produced a specific inhibitor of the catalytic activity of Bcr-Abl called STI571. This drug was shown to eliminate Bcr-Abl-positive cells both in vitro and in vivo, although resistant cells may appear in culture and relapse occurs in some patients. In the study described here, Bcr-Abl-positive cells treated with tyrosine-kinase inhibitors such as herbimycin A, genistein or STI571 lost their phosphotyrosine-containing proteins, but were still extremely resistant to apoptosis. Therefore, in the absence of tyrosine-kinase activity, Bcr-Abl-positive cells continue to signal biochemically to prevent apoptosis induced by chemotherapeutic drugs. We propose that secondary antiapoptotic signals are entirely responsible for the resistance of Bcr-Abl-positive cells. Precise determination of such signals and rational drug development against them should improve the means to combat Ph chromosome-positive leukemia.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Fusión bcr-abl/metabolismo , Piperazinas/farmacología , Proteínas Tirosina Quinasas/metabolismo , Pirimidinas/farmacología , Benzamidas , Benzoquinonas , Western Blotting , Caspasas/metabolismo , Resistencia a Antineoplásicos , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Genisteína/farmacología , Células HL-60/efectos de los fármacos , Células HL-60/metabolismo , Humanos , Mesilato de Imatinib , Células K562/efectos de los fármacos , Células K562/metabolismo , Lactamas Macrocíclicas , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinonas/farmacología , Rifabutina/análogos & derivados , Factores de TiempoRESUMEN
Glucocorticoid gene regulation can be carried out through direct binding of glucocorticoid receptor to glucocorticoid responsive elements (GRE), regulating directly gene transcription and modulating some signaling pathways. The human immunodeficiency virus type 1 (HIV-1) expression can be activated by different immunomodulators through binding of particular nuclear factors to its long terminal repeat (LTR). In order to investigate the effect of glucocorticoids in pathways that activate HIV-1 expression, we transfected promonocyte (U937) and T lymphocyte (CEM-T4) cell lineages with a plasmid containing the chloramphenicol acetyl transferase (CAT) reporter gene under the control of the HIV-1 LTR. In U937 cells, dexamethasone (DEX) downregulates CAT expression induced by either phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNFalpha) or granulocyte/macrophage-colony stimulating factor (GM-CSF). In CEM-T4 cells the CAT activity was slightly upregulated by DEX following the induction by either PMA or TNFalpha. Interestingly, in both cell lines transactivation of this reporter gene by transactivator protein (TAT) was downregulated by DEX. When the CAT gene was under control of HIV-1 enhancer isolated from its LTR background, the CAT activity induced by PMA was not affected by the presence of glucocorticoids. In all experiments, comparable data were obtained when DEX was replaced by hydrocortisone (HC). Our results show that, depending on the cell line, glucocorticoids can differently affect HIV-1 expression, probably by interfering in cellular pathways involved in virus expression. Moreover, the target of this regulation in LTR is probably not the enhancer region itself.
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Dexametasona/farmacología , Regulación Viral de la Expresión Génica/efectos de los fármacos , Glucocorticoides/farmacología , Duplicado del Terminal Largo de VIH/efectos de los fármacos , VIH-1/genética , Hidrocortisona/farmacología , Línea Celular , Cloranfenicol O-Acetiltransferasa/genética , Cloranfenicol O-Acetiltransferasa/metabolismo , Genes Reporteros , Humanos , Monocitos , Receptores de Glucocorticoides/metabolismo , Proteínas Recombinantes/metabolismo , Linfocitos T , Acetato de Tetradecanoilforbol/farmacología , Transactivadores/metabolismo , Activación Transcripcional/efectos de los fármacos , Transfección , Factor de Necrosis Tumoral alfa/farmacología , Células U937RESUMEN
OBJECTIVE: The features of achondroplasia, the most common form of dwarfism, includes short cranial base and midface hypoplasia; both abnormalities increased the risk of upper airway obstruction during sleep. The aim of our study was to evaluate sleep and respiratory function of children with achondroplasia and to differentiate central from obstructive apnea. We also wanted to correlate apneic events with foramen magnum stenosis. STUDY DESIGN: Sixteen children with achondroplasia (mean age, 4.7 years) were studied by noctumal polysomnography and brain computed tomography or magnetic resonance imaging. A comparison of sleep and respiratory findings was made between the study group and 25 children with adenotonsillar hypertrophy. RESULTS: The study revealed no significant difference between groups with respect to sleep architecture. We also found no relationship between apnea type and foramen magnum stenosis. Twelve children (75%) with achondroplasia had significant upper airway obstruction during sleep, with symptoms of continuous snoring and periods of brief obstructive apnea, hypopnea, or both. The mean apneahypopnea index (per hour of sleep) did not differ significantly between the two groups. However, the breathing rate during sleep was increased in children with achondroplasia. These findings indicate that the most important breathing disorder during sleep in children with achondroplasia is upper airway obstruction. CONCLUSION: We conclude that polysomnography with detailed scoring of breathing abnormalities is a useful tool in evaluating sleep-disordered breathing in children with achondroplasia.
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Acondroplasia/fisiopatología , Obstrucción de las Vías Aéreas/fisiopatología , Síndromes de la Apnea del Sueño/fisiopatología , Acondroplasia/complicaciones , Obstrucción de las Vías Aéreas/complicaciones , Obstrucción de las Vías Aéreas/etiología , Niño , Preescolar , Electromiografía , Femenino , Humanos , Lactante , Masculino , Polisomnografía , Síndromes de la Apnea del Sueño/etiologíaRESUMEN
H-Y antigen, the proposed inducer of testicular organogenesis, was determined serologically in 3 patients with male pseudohermaphroditism due to Leydig cell hypoplasia, a pathological model with lack of Leydig cell differentiation but normal seminiferous tubule embryogenesis. One patient was the offspring of consanguineous parents and 2 siblings presented as women with a lack of breast development and primary amenorrhea. Gonads were palpable in the inguinal canal, except for the right intra-abdominal testis in 1 patient. Two patients had female external genitalia and 1 had partial labial fusion. Karyotypes were 46XY. Gonadotropin levels were elevated, and testosterone was low and failed to increase after stimulation with human chorionic gonadotropin. Testosterone precursors were not elevated. Testicular histology showed absence of mature Leydig cells but relatively preserved seminiferous tubules. Family history was consistent for autosomal recessive inheritance. H-Y antigen expression measured by an enzyme-linked immunosorbent assay was normal, indicating that lack of other inductive factors for Leydig cell differentiation are responsible for Leydig cell hypoplasia.
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Trastornos del Desarrollo Sexual/diagnóstico , Antígeno H-Y/análisis , Células Intersticiales del Testículo/patología , Adulto , Diferenciación Celular , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Genes Recesivos , Humanos , Cariotipificación , Masculino , Testículo/patologíaRESUMEN
Gc allele frequencies were determined in Haitian immigrants, a group at high risk for AIDS. Gc2, an allele associated with disease resistance, is infrequent in this group; Gc1f is frequent.
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Síndrome de Inmunodeficiencia Adquirida/genética , Alelos , Frecuencia de los Genes , Proteína de Unión a Vitamina D/genética , Haití/etnología , Humanos , Factores de Riesgo , Estados UnidosAsunto(s)
Riñón/fisiopatología , Enfermedad Mixta del Tejido Conjuntivo/fisiopatología , Adolescente , Adulto , Anticuerpos Antinucleares/análisis , Autoanticuerpos/análisis , Cloroquina/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedad Mixta del Tejido Conjuntivo/inmunología , Prednisona/uso terapéutico , Ribonucleoproteínas/inmunologíaRESUMEN
A doenca mista do tecido conjuntivo (DMTC) descrita por Sharp em 1969, e caracterizada por uma superposicao clinica de lupus eritematoso sistemico (LES), miosite (PM-DM), esclerose sistemica progressiva(ESP) e artrite reumatoide (AR); presenca de altos titulos de anticorpos anti-RNP, ausencia de anticorpos anti-DNA-nativo, baixa frequencia de comprometimento renal e bom prognostico sob o uso de doses baixas de esteroides. Neste estudo, oito pacientes com esta doenca foram seguidos evolutivamente, durante tres anos, em relacao aos aspectos clinicos e laboratoriais. Os demais permanecem com quadro clinico de LES ou DMTC. Nenhum deles evoluiu para ESP. Os estudos laboratoriais nao mudaram significativamente. Os autores concluiram que a DMTC pode ser considerada como uma sindrome isolada no grupo das doencas difusas do tecido conectivo